Nonpeptidyl platelet aggregation inhibitors having specificity for the GPIIb III.sub. receptor

ABSTRACT

A benzodiazepinedione derivative which acts as a nonpeptidyl platelet aggregation inhibitor is provided. This inhibitor potently inhibits fibrinogen binding to the GPII b  III a  receptor and is provided in therapeutic compositions for the treatment of diseases for which blocking platelet aggregation is indicated. These nonpeptidyl inhibitors are provided in combination with thrombolytics and anticoagulants.

This application is a continuation-in-part application of co-pendingU.S. Ser. No. 07/781,477, filed Oct. 18, 1991 now abandoned.

FIELD OF THE INVENTION

The present invention relates to nonpeptidyl inhibitors of plateletaggregation. Specifically, the invention is directed to antagonists ofthe final common pathway of platelet aggregation. These antagonists actas potent antithrombotics. The invention further relates to therapeuticapplications of these nonpeptidyl inhibitors in diseases for whichblocking platelet aggregation is indicated.

BACKGROUND OF THE INVENTION

A. Platelets

Platelets are particles found in whole blood that initiate and providethe structural basis for the hemostatic plug necessary to stop bleeding.Platelets depend on adhesive interactions with extracellular proteinsand other cells for proper function (see Hawiger, J. AtherosclerosisReviews 21:165-186 (1990) and Roth J. R. Innunology Today 13(2):100-105(1992)). The external platelet plasma membrane surface is covered with avariety of membrane bound glycoproteins, many of which have adhesivefunctions. Perhaps the most abundant platelet membrane adhesive proteinsbelong to the integrin superfamily which include the glycoproteins;GPII_(b) III_(a), GPI_(a) II_(a), GPI_(c) II_(a), GPI_(b) IX, and thefibronectin and vitronectin receptors. Each integrin receptor is an αβheterodimer displaying characteristic affinity and specificity towardvarious protein ligands found in serum and/or the extracellular matrixincluding; von Willebrand factor (vWF), collagen, entactin, tenascin,fibronectin (Fn), vitronectin (Vn), and laminin, as well as fibrinogen(Fg) and thrombospondin (see Kieffer et al., Ann. Rev. cell Biol.6:329-357(1990) and Ruoslahti, J. Clin. Invest., 87:1-5 (1991)). Themost abundant integrin found on the surface of normal platelets isGPII_(b) III_(a) comprising about 50,000 molecules per platelet andrepresenting about 2% of the total platelet protein. GPII_(b) III_(a) isa non-covalent, calcium ion dependent heterodimeric complex (Jennings,et al., J. Biol. Chem. 257: 10458 (1982)) that is restricted indistribution to platelets and other cells of the megakaryocytic lineage(Kieffer et al., supra). On activated platelets, GPII_(b) III_(a)promiscously binds a number of protein ligands with varying affinities,including; fibrinogen, fibronectin, von Willebrand factor, vitronectinand thrombospondin (Plow et al., Biochemistry of Platelets, Phillips andShuman eds., p. 225-256, Orlando: Academic Press [1986]). Each of theseprotein ligands contain at least one tripeptide sequence Arg-Gly-Aspwhich is commonly referred to as the "recognition sequence". It isbelieved the most important interactions mediating platelet aggregationinvolve GPII_(b) III_(a) binding with the trinodular fibrinogen and, toa lesser extent, with the filamentous von Willebrand factor (Kieffer etal., supra and Albeda et al., The FASEB Journal, 4:2868-2880 [1990]).

GPII_(b) III_(a) binding to its natural ligands can be inhibited tovarying degrees by peptides and proteins containing the amino acidrecognition sequences; Arg-Gly-Asp (RGD) (Ruoslahti, supra and EPO0368486, assigned to Merck & Co.), Lys-Gly-Asp (KGD), and the fibrinogenγ-chain carboxyterminal dodecapeptide HHLGGAKQAGDV and analogues thereof(Timmons et al., Biochemistry, 28:2919-2922 [1989]).

B. The Hyperthrombotic State

Many common human disorders are characteristically associated with ahyperthrombotic state leading to intravascular thrombi and emboli. Theseare a major cause of medical morbidity, leading to infarction, strokeand phlebitis, and of mortality from stroke and pulmonary and cardiacemboli. Patients with atherosclerosis are predisposed to arterialthromboembolic phenomena for a variety of reasons. Atheroscleroticplaques form niduses for platelet plugs and thrombi that lead tovascular narrowing and occlusion, resulting in myocardial and cerebralischemic disease. This may happen spontaneously or following proceduressuch as angioplasty or endarterectomy. Thrombi that break off and arereleased into the circulation cause infarction of different organs,especially the brain, extremities, heart and kidneys.

In addition to being involved in arterial thrombosis, platelets may alsoplay a role in venous thrombosis. A large percentage of such patientshave no antecedent risk factors and develop venous thrombophlebitis andsubsequent pulmonary emboli without a known cause. Other patients whoform venous thrombi have underlying diseases known to predispose them tothese syndromes. Some of these patients may have genetic or acquireddeficiencies of factors that normally prevent hypercoagulability, suchas antithrombin-3. Others have mechanical obstructions to venous flow,such as tumor masses, that lead to low flow states and thrombosis.Patients with malignancy have a high incidence of thrombotic phenomenafor unclear reasons. Antithrombotic therapy in this situation withcurrently available agents is dangerous and often ineffective.

Patients whose blood flows over artificial surfaces, such as prostheticsynthetic cardiac valves or through extracorporeal perfusion devices,are also at risk for the development of platelet plugs, thrombi andemboli. It is standard practice that patients with artificial cardiacvalves be treated chronically with anti-coagulants. However, in allinstances, platelet activation and emboli formation may still occurdespite adequate anticoagulation treatment.

Thus, a large category of patients, including those withatherosclerosis, coronary artery disease, artificial heart valves,cancer, and a history of stroke, phlebitis, or pulmonary emboli, arecandidates for limited or chronic antithrombotic therapy. The number ofavailable therapeutic agents is limited and these, for the most part,act by inhibiting or reducing levels of circulating clotting factors.These agents are frequently not effective against the patient'sunderlying hematologic problem, which often concerns an increasedpropensity for platelet aggregation and adhesion. They also cause thepatient to be susceptible to abnormal bleeding. Available antiplateletagents, such as aspirin, inhibit only part of the platelet activationprocess and are therefore often inadequate for therapy and also causethe patient to be susceptible to abnormal bleeding.

C. Therapeutic Agents

An agent which effectively inhibits the final common pathway of plateletactivation, namely fibrinogen binding to the GP II_(b) III_(a) receptor,should accordingly be useful in a large group of disorders characterizedby a hyperthrombotic state as described above.

Such agents include anti-thrombotic peptides and pseudopeptides capableof inhibiting platelet aggregation. Ruoslahti et al. (U.S. Pat. No.4,578,079) suggest that tetrapeptides containing the RGD sequence may beused to effect platelet aggregation. Zimmerman et al. (U.S. Pat. No.4,683,291) disclose that positively charged amino acid residues (e.g.Arg and Lys) and homologues located before or toward the amino terminusof the RGD sequence are superior for inhibiting fibrinogen-plateletbinding. Adams et al. (U.S. Pat. No. 4,857,508) describe superiorresults for in-vitro inhibition of human platelet aggregation inplatelet-rich plasma for linear tetrapeptides containingO-methyl-Tyr-amide immediately following the RGD (or homo-RGD) sequence.Tjoeng et al. (U.S. Pat. No. 4,879,313) describe peptide mimeticplatelet aggregation inhibitors in which the first two residues of theRGD sequence are replaced by the pseudodipeptidyl, 8-guanidino-octanoylmoiety. Other peptidomimetics in which the Arg of the RGD sequence hasbeen altered include; WO89/07609 (homo-Arg[Har]), EP 341 915 (Har andalkyl-Arg), WO90/15620 (Har and amidino derivatives e.g. imidazolinyl,imidazolyl, and substituted imidazolyl), EP 422 937 (aryl-, arylalkyl-,and cycloalkyl-amines), WO91/07976 (alkylamidino and alkylaminoderivatives), and WO91/04247 (alkylamino and alkylguanidino prolinederivatives). See also EP 384 362 (glycine derivatives) and EP 381 033.

Complete replacement of all residues in the RGD sequence has beendescribed in EP 372 362 where platelet aggregation inhibitors that arederivatives of benzoic and phenylacetic acid are presented. A benzoicacid derivative inhibitor having a particular low IC₅₀ in an ELISAmeasurement of fibrinogen GPII_(b) III_(a) binding is: ##STR1##

D. Benzodiazepines

It is well established that benzodiazepines and related ligands interactwith a specific site commonly referred to as the "benzodiazepinereceptor" that is associated with a neuro-inhibitory postsynaptic GABAreceptor and a chloride ionophore channel (see e.g. Watjen et al., J.Med. Chem. 32:2282-2291[1989]). Binding of ligands to this receptor isknown to produce a wide variety of nero-physiological effects.Benzodiazepines have not been reported to have platelet aggregationinhibition activity. The preparation and therapeutic use ofbenzodiazepines is described in, for example; EP 0 059 390, EP 0 059386, and EP 0 394 101.

Benzodiazepinediones have been employed as intermediates in thesynthesis of various anti-HIV-1 compounds. For example Kukla, M. J. etal. J. Med. Chem. 34:3187-3197 (1991) reduce the dilactam to either thecorresponding "-one" or diamine in the preparation of various TIBOderivatives having anti-HIV activity.

E. Objects

It is an object of this invention to produce nonpeptidyl compoundshaving potent antithrombotic activity. It is another object of theinvention to produce such compounds that are essentially free of peptidebonds, substantially rigid, and stable to degradation. It is a furtherobject to produce potent nonpeptidyl antithrombotics that specificallyinhibit the GPII_(b) III_(a) -Fg interaction but do not strongly inhibitother RGD sensitive integrin interactions including the Vn-VnR, Fn-FnR,and GPII_(b) III_(a) -vWF interactions. It is still a further object toproduce potent nonpeptidyl platelet aggregation inhibitors that do notsignificantly increase cutaneous bleeding time or diminish otherhemodynamic factors. These and other objects of this invention will beapparent from consideration of the invention as a whole.

SUMMARY OF THE INVENTION

The objects of this invention are accomplished by providing anonpeptidyl platelet aggregation inhibitor comprising a compoundrepresented by structural formula I: ##STR2## where the partialstructure ##STR3## represents; ##STR4## where R¹ and R² are one to threeoptional groups typically selected from; hydrogen, halo(F, Cl, Br, I),cyano, carboxamido, carbamoyloxy, formyloxy, formyl, azido, nitro,ureido, thioureido, hydroxy, mercapto, sulfaonamido, and an optionallysubstituted radical selected from; C₁ -C₁₂ alkyl, C₂ -C₁₂ alkenyl, C₃-C₁₂ alkynyl, C₃ -C₁₂ cycloalkyl, C₆ -C₁₄ aryl, C₆ -C₁₀ aryl-C₁ -C₈-alkyl, C₁ -C₁₂ alkyloxy, C₆ -C₁₄ aryloxy, C₁ -C₁₂ acylamino, N, N-di(C₁-C₁₂)acylamino, N-(C₁ -C₁₂)alkyl-N-(C₁ -C₁₂)-acylamino, C₁ -C₁₂alkylsulfonamido, N-(C₁ -C₁₂)-alkyl-N-(C₁ -C₁₂)alkyl-sulfonylamino, C₁-C₁₂ alkylthiocarbonyl, C₁ -C₁₂ alkylthio, C₁ -C₁₂ alkylsulfinyl, C₁-C₁₂ alkylsulfonyl, C₁ -C₁₂ alkylsulfonato, N-(C₁ -C₁₂)alkylsulfonamido,N,N-di-(C₁ -C₁₂) sulfonamido, N-(C₁ -C₁₂ ) alkyl-N-thioformylamino, C₁-C₁₂ thioacylamino, N-(C₁ -C₁₂)alkyl-N-(C₁ -C₁₂) thioacylamino, C₁ -C₁₂alkylsulfinamido, N-(C₁ -C₁₂)alkyl-N-(C₁ -C₁₂)alkylsulfinylamino, C₁-C₁₂ carbalkoxy, C₁ -C₁₂ alkylcarbonyl, C₁ -C₁₂ alkanoyloxy, N-(C₁-C₁₂)alkylcarboxamido, N,N-di-(C₁ -C₁₂)carboxamido, N-(C₁ -C₁₂)alkylcarbamoyloxy, N,N-di-(C₁ -C₁₂)carbamoyloxy, and heterocycloalkyl orheteroaryl having from 1 to 3 rings, each ring having from 5 to 7 atomswith from 0-3 heteroatoms selected from N, O, and S, provided that atleast one ring contains a heteroatom, where the substituents aretypically selected from halo (F, Cl, Br, I), cyano, azido, nitro,hydroxy, mercapto, sulfonamido, ureido, thioureido, carboxamido,carbamoyloxy, formyloxy, formyl, C₁ -C₄ alkyl, C₁ -C₄ alkoxy, phenyl,and phenoxy.

Y¹, Y², Y³, Y⁴ and Y⁵ are independently selected from CH, CR¹, CR², andN; X is O or S; and Z¹ is selected from CH₂, NH, S, and O;

Q¹ is a substituted or unsubstituted positively chargednitrogen-containing moiety. Preferably Q¹ is selected from:

(A) an amino group including;

(1) --NH₂,

(2) --NR³ H,

(3) --NR³ R⁴, and

(4) --NR³ R⁴ R⁵,

where R³, R⁴, and R⁵ are typically selected from; (i) an optionallysubstituted radical selected from (a) --NR⁶ R⁷, (b) --C(═NR⁸)--NR⁶ R⁷,(c) --N═CR⁹ --NR⁶ R⁷, (d) --NR¹⁰ --CR⁹ ═NR⁸, and (e) --NR¹⁰--C(═NR⁸)--NR⁶ R⁷ where each R⁶, R⁷, R⁸, R⁹, and R¹⁰ is independentlyselected from hydrogen, C₁ -C₄ alkoxy, C₁ -C₄ alkyl, and halo(F, Cl, Br,I)-C₁ -C₄ alkyl, (ii) optionally substituted C₁ -C₁₂ alkyl, (iii)optionally substituted C₃ -C₇ alkenyl, (iv) optionally substituted C₃-C₇ alkynyl, (v) optionally substituted C₃ -C₁₂ cycloalkyl, (vi)optionally substituted C₅ -C₁₂ cycloalkenyl, (vii) optionallysubstituted C₆ -C₁₄ aryl, (viii) optionally substituted C₁ -C₆ alkyl-C₆-C₁₄ -aryl, (ix) optionally substituted C₃ -C₆ alkenyl-C₆ -C₁₀ aryl, (x)optionally substituted heterocyclyl, (xi) optionally substituted C₁ -C₆alkyl-heterocyclyl, (xii) optionally substituted C₁ -C₈ alkoxy, (xiii)optionally substituted C₁ -C₈ thioalkoxy, (xiv) optionally substitutedC₃ -C₁₀ alkenoxy, and (xv) optionally substituted C₆ -C₁₄ aryloxy, wherethe substituents are usually one to three R¹¹, each R¹¹ typicallyselected from (a) optionally substituted C₆ -C₁₂ aryloxy, (b) optionallysubstituted C₆ -C₁₂ arylamino, (c) optionally substituted C₆ -C₁₂ aroyl,(d) optionally substituted C₆ -C₁₂ arylthio, where the substituents areusually one to three R¹², each R¹² typically selected from nitro, amino,C₁ -C₈ alkylamino, di-(C₁ -C₈) alkylamino, amidino, aminomethyleneimino,imino, imino-C₁ -C₄ alkyl, iminomethyleneamino, guanidino, C₆ -C₁₀arylamino, C₁ -C₈ acylamino, C₁ -C₄ alkylsulfonamino, azido, cyano,hydroxy, hydroxy-C₁ -C₈ -alkyl, C₁ -C₈ -alkoxy, phenyloxy, C₁ -C₈alkanoyloxy, C₁ -C₈ alkanoyl, C₆ -C₁₂ aroyl, benzamido, phenyl, halo(F,Cl, Br, I), halo-C₁ -C₈ -alkyl, and C₁ -C₈ -alkyl, (e) C₁ -C₈ alkoxy (f)C₁ -C₈ alkthio (g) halo(F, Cl, Br, I), (h) hydroxy, (i) mercapto, (j) C₁-C₈ alkylcarbonyl, (k) carbamoyl, (l) formyl, (m) formyloxy, (n)carboxy, (o) carb-C₁ -C₈ alkyloxy, (p) C₁ -C₈ alkanoyloxy, (q) N-(C₁-C₈)-alkylcarboxamido, (r) N-(C₁ -C₈), N-(C₁ -C₈)-dialkylcarboxamido,(s) carbamoyloxy, (t) N-(C₁ -C₈) alkylcarbamoyloxy, (u) N-(C₁ -C₈),N-(C₁ -C₈)dialkylcarbamoyloxy, (v) C₁ -C₈ alkylsulfinyl, (w) C₁ -C₈alkylsulfonyl, (x) C₁ -C₈ alkylsulfonato, (y) sulfo, (z) sulfonamido,(aa) N-(C₁ -C₈) alkylsulfonamido, (ab) N-(C₁ -C₈), N-(C.sub. 1 -C₈)dialkylsulfonamido, (ac) amino, (ad) C₁ -C₈ alkylamino, (ae) C₁ -C₈dialkylamino, (af) C₁ -C₈ acylamino, (ag) N-(C₁ -C₈), N-(C₁-C₈)-diacylamino, (ah) N-(C₁ -C₈)-alkyl-N-(C₁ -C₈)-acylamino, (ai)formylamino, (aj) ureido, (ak) isothioureido, (al) amino-C₂ -C₈alkylthio, (am) amino-C₂ -C₈ alkloxy, (an) amidino,(ao) guanidino, (ap)aminomethyleneimino, (aq) imino, (ar) imino-C₁ -C₄ alkyl, (as)iminomethyleneamino, (at) glycylamino, (au) glycyl,(av) phthalimido,(aw) succinimido, (ax) morpholino, (ay) C₁ -C₈ alkylsulfonamido, (az)N-(C₁ -C₈)-alkyl-N-(C₁ -C₈) alkyl sulfonoylamino, (ba) C₁ -C₈alkylsulfinamino, (bb) N-(C₁ -C₈) alkyl-N-(C₁ -C₈) alkylsulfinamino,(bc) C₁ -C₈ alkoxyamino, (bd) C₁ -C₈ alkoxyamino, (be) N-(C₁ -C₈)alkyl-N-(C₁ -C₈) alkoxyamino, (bf) C₃ -C₇ cycloalkyl, and (bg)heterocyclyl, optionally any one or two pairs of R³ - R¹⁰ mayindependently be joined to form one or two optionally substitutedheterocyclic rings, each ring optionally fused with one or twooptionally substituted homocyclic or heterocyclic rings of from four toseven atoms where any heterocyclic ring contains from one to fourheteroatoms selected from N, O, and S and where any ring may besubstituted with from one to three R¹²,

(B) an amidino (aminoiminomethyl) group including;

(1) --C(═NH)--NH₂,

(2) --C(═NH)--NHR³,

(3) --C(═NR⁴)--NHR³,

(4) --C(═NH)--NR³ R⁴, and

(5) --C(═NR⁵)--NR³ R⁴,

where R³, R⁴, and R⁵ are defined above,

(C) an aminoalkyleneamino group including;

(1) --N═CH--NH₂,

(2) --N═CH--NHR³,

(3) --N═CH--NR³ R⁴, and

(4) --N═CR⁵ --NR³ R⁴,

where R³, R⁴, and R⁵ are defined above,

(D) an iminoalkyleneamino group, including;

(1) --NH--CH═NH,

(2) --NH--CH═NR³,

(3) --NH--CR⁴ ═NR³, and

(4) --NR⁵ --CR⁴ ═NR³,

where R³, R⁴, and R⁵ are defined above,

(E) a guanidino (aminoiminomethyleneamino) group including;

(1) --NH--C(═NH)--NH₂,

(2) --NH--C(═NH)--NR³ H,

(3) --NH--C(═NH)--NR³ R⁴,

(4) --NH--C(═NR⁵)--NR³ R⁴,

(5) --NR³ --C(═NR³)--NR³ R⁴,

(6) --NR³ --C(═NH)--NR³ R⁴,

(7) --NR³ --C(═NR³)--NH₂,

(8) --NR³ --C(═NH)--NH₂,

(9) --NR³ --C(═NR³)--NHR⁴, and

(10) --NR³ --C(═NH)--NHR⁴,

where R³, R⁴, and R⁵ are defined above,

(F) an optionally substituted saturated heterocyclic group including;##STR5## where (1) n is 0, 1, 2, or 3, (2) R¹³ is selected from; R⁶,--CR⁹ (═NR⁸)--NR⁶ R⁷, --C(═NR⁸)--NR⁶ R⁷, --N═CR⁹ --NR⁶ R⁷, --NR¹⁰ --CR⁹═NR⁸, and-NR¹⁰ --(C═NR⁸)--NR⁶ R⁷ where R⁶ -R¹⁰ are defined above, (3) Z²is O, S, or NR¹³, and (4) the substituents are independently one tothree R¹², (G) an optionally substituted unsaturated (nonaromatic)heterocyclyl including; ##STR6## where (1) m is 1, 2, or 3, (2) Z² andR¹³ are defined above, and (3) the substituents are typically one tothree R¹²,

(H) an optionally substituted unsaturated (aromatic) heterocyclylincluding; ##STR7## where (1) Z³, Z⁴, and Z⁵ are typically selected fromO, S, N, and NH, provided at least one Z³, Z⁴, or Z⁵ is N or NH, (2) R¹³is defined above, and the substituents are independently one to threeR¹²,

(I) an optionally substituted bicycloheterocyclic group including;##STR8## where the partial structure ##STR9## represents ##STR10## whereZ⁷, Z⁸, and Z⁹ are independently selected from; ##STR11## provided thatat least one Z⁷, Z⁸, or Z⁹ is ##STR12## where (1) o is 0, 1, or 2, (2)R¹³ is defined above, and (3) the substituents are independently one tothree R¹². Exemplary heterocyclic Q¹ groups include; isoindolinyl,quinuclidinyl, morpholinyl, and 1,3-diazacyclohex-4-ene. Optionally, anyof the nitrogen containing heterocycles described above may besubstituted with amino, imino, amidino, aminomethyleneimino,iminomethyleneamino, guanidino, N^(G) -aminoguanidino, alkylamino,dialkylamino, trialkylamino, or alkylideneamino groups.

L¹ is a bivalent radical containing from 3 to 9 methylene groups whereany methylene group or groups may be replaced with one or more alkene,alkyne, aryl, or functional groups containing the heteroatoms selectedfrom the group N, O, and S. Preferably, L¹ is a saturated orunsaturated, linear, branched, or cyclic bivalent radical separating Qfrom the 7 carbon of the benzodiazepinedione nucleus. Typically, theheteroatoms (N, O, and S) will comprise from 0-5 of the atoms separatingQ from the benzodiazepinedione nucleus. Preferably, L¹ is typically anoptionally substituted bivalent radical including; (A) C₃ -C₇ -alkylene,(B) C₃ -C₇ -cycloalkylene, (C) C₃ -C₇ -alkenylene, (D) C₃ -C₇-alkadienylene, (E) C₃ -C₇ -alkynylene, (F) C₄ -C₇ -alkadiynylene, (G)C₄ -C₇ -alkenynylene, (H) C₆ -C₁₄ -arylene, (I) C₆ -C₁₄ -aryl-C₂ -C₄-alkynylene, (J) C₁ -C₃ -alkyl-C₆ -C₁₄ -aryl-C₂ -C₄ -alkynylene, (K) C₆-C₁₄ -aryl-C₂ -C₄ -alkenylene, (L) C₁ -C₃ -alkyl-C₆ -C₁₄ -arylene, (M)C₁ -C₃ -alkyl-C₆ -C₁₄ -aryl-C₂ -C₄ -alkenylene, (N) C₆ -C.sub. 14-aryl-C₁ -C₃ -alkylene, (O) C₆ -C₁₄ -aryl-C₁ -C₃ -alkyloxyene, (P) C₁-C₂ -alkyl-C₆ -C₁₄ -aryl-C₁ -C₂ -alkylene, (Q) C₁ -C₃ -alkyloxy-C₆ -C₁₄-arylene, (R) C₂ -C₆ -alkyloxyene, (S) C₁ -C₅ -alkyloxy-C₁ -C₅-alkylene, (T) C₆ -C₁₀ -aryloxyene, (U) C₆ -C₁₀ -aryloxy-C₁ -C₅-alkylene, (V) C₂ -C₆ -alkylthioene, (W) C₁ -C₅ -alkylthio-C₁ -C₅-alkylene, (X) C₆ -C₁₀ -arylthioene, (Y) C₆ -C₁₀ -arylthio-C₁ -C₅-alkylene, (Z) C₁ -C₅ -alkylsulfoxide-C₁ -C₅ -alkylene, (AA) C₁ -C₅-alkylsulfone-C₁ -C₅ -alkylene, ##STR13## where (1) R¹⁴ is selectedfrom; (i) a chemical bond, (ii) C₁ -C₅ -alkyl, (iii) C₃ -C₇ -cycloalkyl,(iv) C₂ -C₅ -alkenyl, (v) C₃ -C₅ -alkynyl, (vi) C₆ -C₁₀ -aryl, (vii) C₁-C₂ -alkyl-C₆ -C₁₀ -aryl-C₁ -C₂ -alkyl, (viii) C₁ -C₃ -alkyl-C₆ -C₁₂-aryl, (ix) C₆ -C₁₀ -aryl-C₁ -C₂ -alkyl, (x) C₆ -C₁₀ -aryloxy-C₁ -C₂-alkyl, and (xi) piperizinyl, (2) R¹⁵ is selected from; (i) a chemicalbond, (ii) C₁ -C₄ -alkyl, (iii) C₂ -C₄ -alkenyl, (iv) C₂ -C₄ -alkynyl,(v) C₁ -C₃ -alkyl-C₆ -C₁₂ -aryl, and (vi) C₆ -C₁₀ -aryl, (3) R¹⁶ isselected from; (i) a chemical bond, (ii) C₁ -C₅ -alkyl, (iii) C₃ -C₇-cycloalkyl, (iv) C₃ -C₅ -alkenyl, (v) C₃ -C₅ -alkynyl, (vi) C₆ -C₁₀-aryl, (vii) C₁ -C₃ -alkyl-C₆ -C₁₂ -aryl, (viii) C₆ -C₁₀ -aryl-C₁ -C₂-alkyl, and (ix) piperizinyl, (4) R¹⁷ is selected from; (i) C₃ -C₄-alkenyl, (ii) C₃ -C₄ -alkynyl, (iii) C₆ -C₁₀ -aryl, and (iv) benzyl,(5) HET is a saturated or unsaturated heterocycle having from 5-14 atomsin the cycle(s) and from 1-3 heteroatoms selected from N, O, and S,where the substituents are selected from one to three R¹².

L² is typically an optionally substituted bivalent radical including butnot limited to; ##STR14## where; (1) p is 1, 2, 3 or 4, (2) R⁶, R⁷, o,and HET are defined above, and (3) the substituents are typicallyselected from one to three R¹².

T-U-G is selected from; ##STR15## where; (1) X is defined above, (2)R¹⁸, R¹⁹, R²⁰, R²³, are typically selected from (i) hydrogen, (ii)optionally substituted C₁ -C₁₂ alkyl, (iii) optionally substituted C₃-C₁₂ alkenyl, (iv) optionally substituted C₃ -C₁₄ cycloalkyl, (v)optionally substituted C₁ -C₁₂ alkyl-C₆ -C₁₄ aryl, (vi) optionallysubstituted C₆ -C₁₄ aryl, (vii) optionally substituted C₁ -C₄alkylphenyl, and (viii) optionally substituted C₁ -C₁₂ alkoxy, (3) R²¹and R²² are typically selected from (i) Q² -L³ -where Q² is selectedfrom hydrogen and Q¹, and L³ is either a chemical bond, L¹ or L², (ii)optionally substituted C₁ -C₁₂ -alkyl, (iii) optionally substituted C₆-C₁₄ -aryl, (iv) optionally substituted C₃ -C₁₄ -cycloalkyl, (v)optionally substituted C₁ -C₁₂ -alkyl-C₆ -C₁₄ aryl, and (vi) optionallysubstituted C₁ -C₁₂ -alkyl-C₃ -C₁₄ -cycloalkyl, where the substituentsare usually (a) halo (F, Cl, Br, I), (b) nitro, (c) hydroxy, (d)carboxy, (e) tetrazole, (f) hydroxamate, (g) sulfonamide, (h)trifluoroimide, (i) phosphonate, (j) C₁ - C₆ -alkyl, (k) C₆ -C₁₄ -aryl,(l) benzyl, (m) C₃ -C₁₄ -cycloalkyl, (n) COR²⁴ where R²⁴ is selectedfrom C₁ -C₈ -alkoxy, C₃ -C₁₂ -alkenoxy, C₆ -C₁₂ -aryloxy, di-C₁ -C₈-alkylamino-C₁ -C₈ -alkoxy, acylamino-C₁ -C₈ -alkoxy selected fromacetylaminoethoxy, nicotinoylaminoethoxy, succinamidoethoxy, andpivaloyloxyethoxy, and C₆ -C₁₂ -aryl-C₁ -C₈ -alkoxy where the aryl groupis unsubstituted or substituted with one to three of the groups nitro,halo (F, Cl, Br, I), C₁ -C₄ -alkoxy, amino, hydroxy, hydroxy-C₂ -C₈-alkoxy, and dihydroxy-C₃ -C₈ -alkoxy, and (o) CONR²⁵ R²⁶ where R²⁵ andR²⁶ are typically selected from hydrogen, C₁ -C₁₀ -alkyl, C₃ -C₁₀-alkenyl, C₆ -C₁₄ -aryl, C₁ -C₆ -alkyl-C₆ -C₁₀ -aryl. Optionally, R²⁵and R²⁶ taken together may form trimethylene, tetramethylene,pentamethylene, and 3-oxopentamethylene. Also, optionally, R¹ and R²²taken together may form an optionally substituted 5, 6, or 7 membersaturated or unsaturated homocyclic or heterocyclic ring containing 0-3heteroatoms selected from O, S, and N, where the substituents areselected from R²¹.

D is typically (A) R²¹, or (B)--(C═O)--Xaa, where Xaa is one to three Dor L α-amino acid residues.

W is typically selected from; ##STR16## where (1) R²⁷ is selected from(i) a chemical bond, (ii) methylene, and (iii) ethylene, (2) R²⁸ isselected from the group consisting of (i) hydroxy, (ii) C₁ -C₈ -alkoxy,(iii) C₃ -C₁₂ -alkenoxy, (iv) C₆ -C₁₂ -aryloxy, (v) C₁ -C₆ -alkyl-C₆-C₁₂ -aryloxy, (vi) di-C₁ -C₈ -alkylamino-C₁ -C₈ -alkoxy, (vii)acylamino-C₁ -C₈ -alkoxy selected from the group (a) acetylaminoethoxy,(b) nicotinoylaminoethoxy, and (c) succinamidoethoxy, (viii) C₁ -C₈-alkoyloxy-C₁ -C₈ -alkoxy, (ix) C₆ -C₁₂ -aryl-C₁ -C₈ -alkoxy where thearyl group is unsubstituted or substituted with one to three of thegroups (a) nitro, (b) halo (F, Cl, Br, I), (c) C₁ -C₄ -alkoxy, and (d)amino, (x) hydroxy-C₂ -C₈ -alkoxy, (xi) dihydroxy-C₃ -C₈ -alkoxy, and(xii) NR²⁹ R³⁰ where R²⁹ and R³⁰ are independently selected from thegroup (a) hydrogen, (b) C₁ -C₈ -alkyl, (c) C₃ -C₈ -alkenyl, (d) C₆ -C₁₂-aryl where the aryl group is unsubstituted or substituted with one tothree of the groups nitro, halo (F, Cl, Br, I), C₁ -C₄ -alkoxy, andamino, and (e) C₆ -C₁₂ -aryl-C₁ -C₈ -alkyl where the aryl group isunsubstituted or substituted with one to three of the groups nitro, halo(F, Cl, Br, I), and C₁ -C₄ -alkoxy(3) R³¹ is typically selected from (i)hydrogen, (ii) phenyl, (iii) C₁ -C₄ -alkyl, and (iv) halo(F, Cl, Br,I)-C₁ -C₄ -alkyl.

The invention further provides a pharmaceutical composition comprising apharmaceutically acceptable excipient and/or pharmaceutically acceptablehydrates, solvates, and salts of I.

The invention provides a method for inhibiting platelet aggregation orreducing platelet aggregation in a mammal comprising administering aplatelet aggregation inhibiting amount of the pharmaceutical compositionof I. Optionally, the method includes administering the pharmaceuticalcomposition in combination with a peptidyl antithrombotic and/or athrombolytic agent and/or an anticoagulant.

DETAILED DESCRIPTION OF THE INVENTION

A. Definitions

Terms used in the claims and specification are defined as set forthbelow unless otherwise specified.

As used herein, the term "positively charged" when used to describe themoiety Q (either Q¹ or Q²) means at least 10% of the Q groups arepositively charged at physiological pH. This will normally mean that thepK_(b) of the nitrogen containing moiety will be about 6.9 or higher.

The term "alkyl" means a branched or unbranched, saturated aliphatichydrocarbon radical, having the number of carbon atoms specified, or ifno number is specified, having up to 12 carbon atoms. Examples of alkylradicals include methyl, ethyl, n-propyl, isopropyl, n-butyl, iso-butyl,sec-butyl, tert-butyl, n-pentyl, 2-methylbutyl, 2,2-dimethylpropyl,n-hexyl, 2-methylpentyl, 2,2-dimethylbutyl, n-heptyl, 2-methylhexyl, andthe like. The terms "lower alkyl" and "alkyl of 1 to 6 carbon atoms" aresynonymous and used interchangeably.

The term "cycloalkyl" as used herein refers to a mono-, bi-, ortricyclic aliphatic ring having 3 to 14 carbon atoms and preferably 3 to7 carbon atoms.

The term "alkenyl" means a branched or unbranched hydrocarbon radicalhaving the number of carbon atoms designated containing one or morecarbon-carbon double bonds, each double bond being independently cis,trans, or a nongeometric isomer.

The term "alkynyl" means a branched or unbranched hydrocarbon radicalhaving the number of carbon atoms designated containing one or morecarbon-carbon triple bonds.

The term "aryl" when used alone means a homocyclic aromatic radicalwhether or not fused having the number of carbon atoms designated.Preferred aryl groups include phenyl, napthyl, biphenyl, phenanthrenyl,naphthacenyl, and the like (see e.g. Lang's Handbook of Chemistry (Dean,J. A., ed) 13^(th) ed. Table 7-2 [1985]).

The term "arylalkyl" means one, two, or three aryl groups having thenumber of carbon atoms designated, appended to an alkyl radical havingthe number of carbon atoms designated including but not limited to;benzyl, naphthylmethyl, phenethyl, benzyhydryl (diphenylmethyl), trityl,and the like.

Unless otherwise specified, the terms "heterocyclic group" or"heterocyclic" or "HET" or "heterocyclyl" are used interchangeably asused herein refer to any mono-, bi-, or tricyclic saturated,unsaturated, or aromatic ring having the number of atoms designatedwhere at least one ring is a 5-, 6- or 7-membered ring containing fromone to three heteroatoms selected from the group nitrogen, oxygen, andsulfur provided that at least one heteroatom is nitrogen (Lang'sHandbook of Chemistry, supra). Typically, the 5-membered ring has 0 to 2double bonds and the 6- or 7-membered ring has 0 to 3 double bonds andthe nitrogen or sulfur heteroatoms may optionally be oxidized, and anynitrogen heteroatom may optionally be quarternized. Included in thedefinition are any bicyclic groups where any of the above heterocyclicrings are fused to a benzene ring. Heterocyclics in which nitrogen isthe heteroatom are preferred.

Bivalent radicals L (either L¹, L², or L²) whether branched orunbranched, derived from alkanes, alkenes, alkadienes, alkynes,alkadiynes, and arenes optionally containing O, N and/or S atoms, orhomo- and heterocycles either aromatic or aliphatic, are designated byadding the suffix "ene" to the corresponding monovalent radical. Atomsbearing the free valences may include any C, O, N or S.

"Pharmaceutically acceptable salts" include both acid and base additionsalts.

"Pharmaceutically acceptable acid addition salt" refers to those saltswhich retain the biological effectiveness and properties of the freebases and which are not biologically or otherwise undesirable, formedwith inorganic acids such as hydrochloric acid, hydrobromic acid,sulfuric acid, nitric acid, phosphoric acid and the like, and organicacids such as acetic acid, propionic acid, glycolic acid, pyruvic acid,oxalic acid, maleic acid, maloneic acid, succinic acid, fumaric acid,tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid,methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid,salicyclic acid and the like.

"Pharmaceutically acceptable base addition salts" include those derivedfrom inorganic bases such as sodium, potassium, lithium, ammonium,calcium, magnesium, iron, zinc, copper, manganese, aluminum salts andthe like. Particularly preferred are the ammonium, potassium, sodium,calcium and magnesium salts. Salts derived from pharmaceuticallyacceptable organic nontoxic bases includes salts of primary, secondary,and tertiary amines, substituted amines including naturally occurringsubstituted amines, cyclic amines and basic ion exchange resins, such asisopropylamine, trimethylamine, diethylamine, triethylamine,tripropylamine, ethanolamine, 2-diethylaminoethanol, trimethamine,dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine,hydrabamine, choline, betaine, ethylenediamine, glucosamine,methylglucamine, theobromine, purines, piperizine, piperidine,N-ethylpiperidine, polyamine resins and the like. Particularly preferredorganic non-toxic bases are isopropylamine, diethylamine, ethanolamine,trimethamine, dicyclohexylamine, choline, and caffeine.

The term "prodrug" as used here means a pharmacologically inactivederivative of a parent drug molecule that requires biotransformation,either spontaneous or enzymatic, within the organism to release theactive drug.

B. Utility

The present invention is the result of the unexpected discovery thatsubstituted fused 7-membered "lactam" ring compounds defined by formulaI, especially including 3,4-dihydro-1H-1,4-benzodiazepine-2,5-diones(referred to hereafter as substituted benzodiazepinediones) are capableof inhibiting both platelet aggregation and binding of fibrinogen to theplatelet receptor GPII_(b) III_(a) at concentrations comparable to manyof the more potent anti-aggregatory peptides of the prior art (see e.g.Ali et al. EP 341 915). Thus the compounds described in the presentinvention inhibit the binding of fibrinogen to its receptor onplatelets, GPII_(b) III_(a), and thus prevent the aggregation ofplatelets and the formation of platelet plugs, emboli and thrombi in thecirculatory system in mammals. Thromboembolic disorders have been shownto be directly related to the susceptibility of blood platelets toaggregate. Mammals exposed to medical procedures such as angioplasty andthrombolytic therapy are particularly susceptible to thrombus formation.The compounds of the present invention can be used to inhibit thrombusformation following angioplasty. They may also be used in combinationwith antithrombolytic agents such as tissue plasminogen activator andits derivatives (U.S. Pat. Nos. 4,752,603; 4,766,075; 4,777,043; EP199,574; EP 0238,304; EP 228,862; EP 297,860; PCT WO89/04368; PCTWO89/00197), streptokinase and its derivatives, or urokinase and itsderivatives to prevent arterial reocclusion following thrombolytictherapy. When used in combination with the above thrombolytic agents,the compounds of the present invention may be administered prior to,simultaneously with, or subsequent to the antithrombolytic agent.Mammals exposed to renal dialysis, blood oxygenation, cardiaccatheterization and similar medical procedures as well as mammals fittedwith certain prosthetic devices are also susceptible to thromboembolicdisorders. Physiologic conditions, with or without known cause may alsolead to thromboembolic disorders. Thus, the compounds described hereinare useful in treating thromboembolic disorders in mammals. Thecompounds described herein may also be used as adjuncts to anticoagulanttherapy, for example in combination with aspirin, heparin or warfarinand other anticoagulant agents. The application of the compoundsdescribed herein for these and related disorders will be apparent tothose skilled in the art.

Compounds of this invention are also useful as intermediates generally,or as precursors of inhibitors to GPII_(b) III_(a) or other integrinreceptors and thus in addition to treating cardiovascular disease, thesecompounds may be usefully employed in metastatic disease and bonedisorders such as osteoporosis.

C. Preferred Embodiments

1. Nonpeptidyl GPII_(b) III_(a) Inhibitors

One embodiment of the invention comprises a compound represented byformula I capable of inhibiting binding of the platelet GPII_(b) III_(a)receptor to its native in vivo ligands. Preferred nonpeptidyl inhibitorsinclude compounds represented by structural formulae II-IV: ##STR17##where R¹, R², R²⁰, R²¹, R²², R²⁸, Q¹, L¹ and L² are defined above.

Referring to formulae I-VI the following structural features of theinstant nonpeptidyl antithrombotic inhibitors can be identified:

a. The positively charged Q moiety;

b. The linking moiety L;

c. The flat (usually aromatic) ring A;

d. The 7-member "lactam" ring;

e. Substituents of TUG especially R²² ;

f. The amino acid linking moiety D; and

g. The negatively charged moiety W.

a. Positively charged Q

Suitable groups Q (either Q¹ or Q²) contain one or more nitrogen atomsand have a pK_(b) sufficiently high so that they are at least 10%positively charged at physiological pH. Q may be one or more primary,secondary, tertiary, or quartinary amines or imines either isolated orconjugated with other nitrogen atoms to form groups including but notlimited to; aminomethyleneimino, amidino, and guanidino groups andmultiples thereof. Alternatively, Q may be a saturated or unsaturated(including aromatic) heterocyclic group provided the group bears apositive charge at physiological pH. In one embodiment of the invention,Q is preferably selected from; amino (H₂ N--), imino (═NH), amidino (H₂NC(═NH)--), aminomethyleneamino (H₂ N--CH═N--), iminomethylamino(HN═CH--NH--), guanidino (H₂ N--C(═NH)--NH--), N^(G) -aminoguanidino (H₂N--HN--C(═NH)--NH--), alkylamino (R¹ NH--), dialkylamino (R¹ ₂ N--),trialkylamino (R¹ ₃ N--), alkylideneamino (R¹ ₂ C═N--), pyranyl,pyrrolyl, imadazolyl, pyrazolyl, pyridyl, pyrazinyl, pyrimidinyl,pyridazinyl, indolizinyl, isoindolyl, 3H-indolyl, indolyl, 1H-indazolyl,purinyl, 4 H-quinolizinyl, isoquinolyl, quinolyl, phthalazinyl,naphthyridinyl, quinoxalinyl, quinazolinyl, cinnolinyl, pteridinyl,4aH-carbazolyl, carbazolyl, b-carbolinyl, phenanthridinyl, acridinyl,perimidinyl, phenanthrolinyl, phenazinyl, phenarsazinyl, phenothiazinyl,pyrrolinyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, pyrazolinyl,piperidyl, piperazinyl, indolinyl, isoindolinyl, quinuclidinyl,morpholinyl, and 1,3-diazacyclohex-4-ene, where R¹ is selected from;hydrogen, C₁ -C₆ -alkyl, C₆ -C₁₀ -aryl, and C₃ -C₁₀ -cycloalkyl.Optionally, any of the nitrogen containing heterocycles described abovemay be substituted with amino, imino, amidino, aminomethyleneamino,iminomethylamino, guanidino, N^(G) -amino-guanidino, alkylamino,dialkylamino, trialkylamino, or alkylideneamino groups.

Exemplary preferred Q¹ groups include the following: ##STR18##

Most preferred Q groups are amino, amidino, and guanidino groups.

b. The linking group L

The length of the bivalent radical L appears to be important tobiological activity. By length is meant the distance between the A ringand the first charge bearing N of substituent Q. For example, when the Amoiety is a 5 or 6-member ring [e.g. the benzene moiety of thebenzodiazepinedione nucleus (carbon 7 of Formula II)], suitable lengthsfor bivalent radical L¹ range from about 3 to about 9 methyleneequivalents. L¹ is therefore a bivalent radical containing from 3 to 9methylene groups connecting Q to the number 7 carbon of thebenzodiazepinedione nucleus (or an equivalent position on other 5 or6-member A rings) where any methylene group or groups may be replacedwith one or more or a combination of; alkene, alkyne, aryl, heterocycleor a functional group or groups containing the heteroatoms N, O, and S,so long as the overall length is equivalent to from 3 to 9 methylenegroups. These functional groups include one or more of the following:##STR19## and may be isolated within the linker (e.g. forming ethers,thioethers, ketones, sulfoxides and the like) or combined in anycombination, provided only that the compounds so produced are stable inaqueous solution and do not exceed the above stated length requirements.For example, combining these functional groups produces esters, amides,ureidos, carbamates, carbonates, sulfonamides, sulfoxides, sulfones, andthe like. Preferred lengths for L¹ are from 4 to 6 while most preferredlengths are about 5 methylene equivalents. In counting atoms comprisingL¹, only those atoms sequentially linking Q with ring A are countedexcept when a homo- or heterocycle comprises L¹ in which case the fewestnumber of atoms separating these moieties are counted. Furthermore,given that a bivalent radical is of appropriate length, it is preferredthat it be somewhat rigid, that is, contain one or more sp² or sp atoms.

In the description that follows, the free valence to the left of thepage is bonded to Q, while the free valence to the right is bonded tocarbon 7 of the compound of formula II (or an equivalent position onother 5 or 6-member A rings) Preferred L¹ 's are selected fromsubstituted or unsubstituted; C₃ -C₇ -alkylene, C₃ -C₇ -cycloalkylene,C₃ -C₇ -alkenylene, C₄ -C₇ -cycloalkenylene, C₅ -C₈ -cycloalkadienylene,C₃ -C₇ -alkadienylene, C₃ -C₇ -alkynylene, C₄ -C₇ -alkenynylene, C₆ -C₁₄-arylene, C₆ -C₁₄ -aryl-C₂ -C₄ -alkynylene, C₁ -C₃ -alkyl-C₆ -C₁₄-aryl-C₂ -C₄ -alkynylene, C₆ -C₁₄ -aryl-C₂ -C₄ -alkenylene, C₁ -C₃-alkyl-C₆ -C₁₄ -arylene, C₁ -C₃ -alkyl-C₆ -C₁₄ -aryl-C₂ -C₄ -alkenylene,C₆ -C₁₄ -aryl-C₁ -C₃ -alkylene, C₆ -C₁₄ -aryl-C₁ -C₃ -alkyloxyene, C₁-C₃ -alkyl-C₆ -C₁₄ -aryl-C₁ -C₂ -alkylene, C₁ -C₃ -alkyloxy-C₆ -C₁₄-arylene, C₂ -C₈ -alkyloxyene, C₁ -C₅ -alkyloxy-C₁ -C₅ -alkylene, C₆-C₁₀ -aryloxyene, C₆ -C₁₀ -aryloxy-C₁ -C₅ -alkylene, C₆ -C₁₀-arylthio-C₁ -C₅ -alkylene, ##STR20## where R¹⁴ is selected from; achemical bond, C₁ -C₈ -alkyl, C₃ -C₇ -cycloalkyl C₂ -C₅ -alkenyl, C₃ -C₅-alkynyl, C₆ -C₁₀ -aryl, C₁ -C₃ -alkyl-C₆ -C₁₂ -aryl, C₁ -C₂ -alkyl-C₆-C₁₀ -aryl-C₁ -C₂ -alkyl, C₆ -C₁₀ -aryl-C₁ -C₂ -alkyl, and C₆ -C₁₀-aryloxy-C₁ -C₂ -alkyl. R¹⁵ is selected from; a chemical bond, C₁ -C₄-alkyl, C₂ -C₄ -alkenyl, C₂ -C₄ -alkynyl, C₆ -C₁₀ -aryl, and C₁ -C₃-alkyl-C₆ -C₁₂ -aryl. R¹⁶ is selected from; a chemical bond, C₁ -C₅-alkyl, C₃ -C₇ -cycloalkyl C₃ -C₅ -alkenyl, C₃ -C₅ -alkynyl, C₆ -C₁₀-aryl, C₁ -C₃ -alkyl-C₆ -C₁₂ -aryl, and C₆ -C₁₀ -aryl-C₁ -C₂ -alkyl. Thesubstituents are preferably selected from one to three R¹² definedabove.

More preferred bivalent radicals L¹ are selected from the followinggroups: ##STR21## Most preferred L¹ 's are selected from; ##STR22##where p is 1, 2, 3, or 4; q is 3, 4, 5, 6 or 7; r is 1, 2, 3, 4, or 5; sis 2 or 3. R¹⁴ is selected from; a chemical bond, C₁ -C₅ alkyl, C₃ -C₇-cycloalkyl, C₂ -C₅ -alkenyl, C₃ -C₅ -alkynyl, C₆ -C₁₀ -aryl, C₁ -C₂-alkyl-C₆ -C₁₂ -aryl, C₁ -C₂ -alkyl-C₆ -C₁₀ -aryl-C₁ -C₂ -alkyl, C₆ -C₁₀-aryl-C₁ -C₂ -alkyl, C₆ -C₁₀ -aryloxy-C₁ -C₂ -alkyl, and piperizinyl.R¹⁵ is a chemical bond connecting L¹ to position 7 of thebenzodiazepinedione. R¹⁶ is selected from; C₁ -C₅ -alkyl, C₃ -C₇-cycloalkyl, C₃ -C₅ -alkenyl, C₃ -C₅ -alkynyl, C₆ -C₁₀ -aryl, C₁ -C₃-alkyl-C₆ - C₁₂ -aryl, C₆ -C₁₀ -aryl-C₁ -C₂ -alkyl, and piperizinyl. Forthe foregoing most preferred L¹ 's R¹⁴ and R¹⁶ bond L¹ to Q¹.

Most preferred Q¹ --L¹ -- combinations are selected from; ##STR23##

The length of the bivalent radical L² is also important to biologicalactivity. Here, when the A moiety is a 10-member fused ring [e.g. thenapthalene moiety of the napthadiazepinedione nucleus (carbon 8 ofFormula III)], suitable lengths for bivalent radical L² range from about1 to about 7 methylene equivalents. L² is therefore a bivalent radicalcontaining from 1 to 7 methylene groups connecting Q¹ to the number 8carbon of the napthadiazepinedione nucleus (or an equivalent position onother 10-member A rings) where any methylene group or groups may bereplaced with one or more alkene, alkyne, aryl, heterocycle orfunctional groups containing the heteroatoms N, O, and S, so long as theoverall length is equivalent to 1 to 7 methylene groups. Here, thefunctional groups are the same as described above for L¹ and may becombined in any combination provided again that the compounds producedare stable in aqueous solution and do not exceed the stated lengthrequirements for L². Preferred lengths for L² are from 2 to 4 while mostpreferred lengths are about 3 methylene equivalents.

Preferred L² 's are optionally substituted bivalent radicals selectedfrom; ##STR24## where o is 0, 1 or 2, p is 1, 2, 3 or 4, R⁶ is definedabove, and where the substituents are selected from one to three R¹²groups defined above.

c. Ring A

Preferred A rings include; benzene, napthalene, tetrahydronapthalene,cyclohexane, thiophene, pyridine, pyrazine, pyrimidine, quinoline,isoquinoline, quinoxaline, quinazoline, pteridine, and naphthyridine.The most preferred A ring is benzene.

d. The 7-membered "lactam" ring

Preferred seven member rings are those of formula I where T bears thesubstituent R²². Thus T is preferably sp³ carbon or nitrogen. Alsopreferably G is a methylene group. The most preferred "lactam ring" is adiazepinedione.

e. Substituents of T-U-G

R¹⁹. and R²⁰ are preferably hydrogen or halogen. R¹⁸ and R²¹ arepreferably hydrogen or halogen or taken together form oxo. R²² ispreferably selected from; hydrogen, optionally substituted C₁ -C₆-alkyl, where the substituents are selected from amino, hydroxy, halo(F, Cl, Br, I), carboxy, and C₁ -C₄ -alkoxycarbonyl, optionallysubstituted C₆ -C₁₀ -aryl, and optionally substituted C₆ -C₁₂ -aryl-C₁-C₄ -alkyl, where the substituents on any aryl group are selected fromamino, nitro, halo (F, Cl, Br, I), halo(F, Cl, Br, I)-C₁ -C₆ -alkyl, C₁-C₆ -alkoxy, C₆ -C₁₀ -aryloxy, amino-C₁ -C₆ -acylamino, amino-C₁ -C₆-acyl, and guanidinoC₆ -C₁₀ -aroylamino.

f. The amino acid linking moiety D

D is preferably hydrogen, phenyl, or lower alkyl. Optionally, D is--(C═O)--Xaa, where Xaa is one to three natural, unnatural, or modifiedα-amino acid residues, preferably one or two naturally occurring aminoacid residues, and most preferably a naturally occurring hydrophobicamino acid residue. Optionally, when Xaa is two amino acid residues, theterminal residue is Arg or Lys amide. Common naturally occurring a-aminoacids are described by the standard three letter amino acid code whenreferring to amino acids or residues. When the three-letter code beginswith a lower-case letter, it is understood the amino acid is theunnatural or D-isomeric form. Standard abbreviations are listed in TheMerck Index, 10th Edition, pp Misc-2-Misc-3. Modified or unusual α-aminoacids such as norleucine (Nle) and ornithine (Orn) are designated asdescribed in U.S. Patent and Trademark Office Official Gazette 1114TMOG,May 15, 1990.

g. The negatively charged W moiety

Preferred W's are either a tetrazole or a carboxylate. Preferably thesegroups are represented by; ##STR25## where R²⁷ is methylene, and R²⁸ andR³¹ are hydroxyl and hydrogen respectively. Optionally, R²⁸ and R³¹ aresubstituents that transform compounds represented by structural formulaeI-VI into prodrugs. When W is a carboxylate, preferred prodrug formsinclude simple esters, a-acyloxyalkyl esters, and amides. Preferredesters include compounds where R²⁸ is selected from; ##STR26##

The most preferred compounds of this invention are represented bystructural formula II and are selected from:

1-(4-chlorophenyl)methyl-4-(2-carboxyethyl)-7-(4-(1-piperidin)-phenyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(diphenyl)methyl-4-(2-carboxyethyl)-7-(4-(1-piperidin)-phenyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(m-trifluromethyl)phenyl-4-(2-carboxyethyl)-7-(4-(1-piperidin)-phenyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(4-chlorophenyl)methyl-4-(2-carboxyethyl)-7-(4-(2-aminoethoxy)-phenyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(diphenyl)methyl-4-(2-carboxyethyl)-7-(4-(2-aminoethoxy)-phenyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(m-trifluromethyl)phenyl-4-(2-carboxyethyl)-7-(4-(2-aminoethoxy)-phenyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(diphenyl)methyl-4-(2-carboxyethyl)-7-(6-aminohexyl)-3,4-dihydro-1H-1,4benzodiazapine-2,5-dione,

1-(diphenyl)methyl-4-(2-carboxyethyl)-7-(6-aminohex-1-ynyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(diphenyl)methyl-4-(2-carboxyethyl)-7-(5-aminopentoxy)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,-p01-(diphenyl)methyl-4-(2-carboxyethyl)-7-(5-guanidinopentyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(diphenyl)methyl-4-(2-carboxyethyl)-7-(4-guanidinobutoxy)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(diphenyl)methyl-4-(2-carboxyethyl)-7-(5-aminopent-1-ynyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(diphenyl)methyl-4-(2-carboxyethyl)-7-(5-guanidinopent-1-ynyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(4-chlorophenyl)methyl-4-(2-carboxyethyl)-7-(6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(4-chlorophenyl)methyl-4-(2-carboxyethyl)-7-(5-aminopentoxy)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(2,4-difluorophenyl)methyl-4-(2-carboxyethyl)-7-(4-(1-piperidin)phenyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(2,4-difluorophenyl)methyl-4-(2-carboxyethyl)-7-(4-(2-aminoethoxy)phenyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(2,4-difluorophenyl)methyl-4-(2-carboxyethyl)-7-(6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(2,4-difluorophenyl)methyl-4-(2-carboxyethyl)-7-(5-aminopentoxy)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(4-chlorophenyl)methyl-4-(3-butanoyl)-7-(4-(1-piperidin)-phenyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(diphenyl)methyl-4-(3-butanoyl)-7-(4-(1-piperidin)-phenyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(diphenyl)methyl-4-(3-butanoyl)-7-(6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(diphenyl)methyl-4-(3-butanoyl)-7-(5-aminopentoxy)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(diphenyl)methyl-4-(3-butanoyl)-7-(5-guanidinopentyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(4-chlorophenyl)methyl-4-(3-butanoyl)-7-(6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(2,4-difluorophenyl)methyl-4-(3-butanoyl)-7-(6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(4-chlorophenyl)methyl-4-(3-phenylpropion-3-yl)-7-(4-(1-piperidin)phenyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(diphenyl)methyl-4-(3-phenylpropion-3-yl)-7-(4-(1-piperidin)phenyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(diphenyl)methyl-4-(3-phenylpropion-3-yl)-7-(6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(diphenyl)methyl-4-(3-phenylpropion-3-yl)-7-(5-aminopentoxy)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(diphenyl)methyl-4-(3-phenylpropion-3-yl)-7-(5-guanidinopentyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(4-chlorophenyl)methyl-4-(3-phenylpropion-3-yl)-7-(6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(2,4-difluorophenyl)methyl-4-(3-phenylpropion-3-yl)-7-(6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(3-(butyryl)aminophenyl)methyl-4-(2-carboxyethyl)-7-(6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(3-(butyryl)aminophenyl)methyl-4-(2-carboxyethyl)-7-(5-guanidinopentyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(3-(4-aminobutyryl)aminophenyl)methyl-4-(2-carboxyethyl)-7-(6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(3-(4-guanidinobutyryl)aminophenyl)methyl-4-(2-carboxyethyl)-7-(5-guanidinopentyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(3-(6-aminohexoyl)aminophenyl)methyl-4-(2-carboxyethyl)-7-(6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(3-(6-guanidinohexoyl)aminophenyl)methyl-4-(2-carboxyethyl)-7-(5-guanidinopentyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(3-(6-aminopentoyl)aminophenyl)methyl-4-(2-carboxyethyl)-7-(6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(3-(6-guanidinopentoyl)aminophenyl)methyl-4-(2-carboxyethyl)-7-(5-guanidinopentyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(3-(6-aminopropionyl)aminophenyl)methyl-4-(2-carboxyethyl)-7-(6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(3-(6-guanidinopropionyl)aminophenyl)methyl-4-(2-carboxyethyl)-7-(5-guanidinopentyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(3-(6-aminoacetyl)aminophenyl)methyl-4-(2-carboxyethyl)-7-(6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(3-(6-guanidinoacetyl)aminophenyl)methyl-4-(2-carboxyethyl)-7-(5-guanidinopentyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(3-(4-guanidinobenzoyl)aminophenyl)methyl-4-(2-carboxyethyl)-7-(6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(4-(6-aminopropionyl)aminophenyl)methyl-4-(2-carboxyethyl)-7-(6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,

1-(3-(4-aminobutyl)phenyl)methyl-4-(2-carboxyethyl)-7-(6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione,and

1-(4-carboxyphenyl)methyl-4-(2-carboxyethyl)-7-(6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dione.

D. Methods of Making

Compounds of the present invention can be prepared by many methods,employing standard chemical methodologies described and referenced instandard textbooks (e.g. March, J. "Advanced Organic Chemistry"McGraw-Hill, New York, 1977; Collman, J. P., Hegedus, L. S., Norton, J.R., Finke, R. G. "Principles and Applications of Organotransition MetalChemistry" University Science, Mill Valley, 1987; Larock, R. C."Comprehensive Organic Transformations" Verlag, N.Y., 1989). In thedescription that follows standard abbreviations as recommended by theJournal of Organic Chemistry (see "Guidelines for Authors" in anyvolume) are employed unless otherwise specified.

1. The Q Group

The nitrogen containing substituents Q or a precursor thereof may addedto the linker L and the combination Q--L--, usually in protected form,may be bonded to ring A. Alternatively, Q or Q plus a portion of L maybe added to L or a portion thereof after ring A and the rest of themolecule have been formed. Q itself may be prepared and bonded to ring Aby standard methods published in both the scientific and patentliterature (see e.g. U.S. Pat. Nos. 4,992,542, 4,997,936, 4,194,047,5,003,076, 5,063,207, 5,063,208, and 5,079,357, and references citedtherein).

In the description immediately following, addition of Q--L--to thebenzene moiety of 3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione isspecified. It will be understood that these same procedures may beapplied to other ring systems encompassed by formula I.

2. The benzodiazepinedione

The key intermediate is the substituted3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione 1. The benzodiazepinedione 1(R≠H) may be prepared using a triply convergent approach from theisatoic anhydride 2, the β-alanine ester 3, and the α-haloacetyl halide4 (Scheme 1). The benzodiazepinedione 1 (R=H) may be prepared using adoubly convergent approach from the isatoic anhydride 2 (R=H) and thesubstituted N-carboxymethyl β-alanine ester 5 (Scheme 2).

Methods for preparation of the isatoic anhydrides 2, β-alanine esters 3,and α-halo acetyl halides 4 (Scheme 1), are known in the art and anumber of them are available from commercial sources such as AldrichChemical Co. A reaction sequence, similar to that shown in Scheme 1 toprepare 3,4-dihydro-1H-1,4-benzodiazepine-2,5-diones has been previouslydescribed (Lee, C. M. J. Heterocyclic Chem. 1964, 1, 235). Briefly, theisatoic anhydrides are converted to N-(2-aminobenzoyl)-β-alanine esters6 by allowing 2 to react with 3, or its salt, in the presence an organicbase. The isatoic anhydride 2 may be substituted or unsubstituted, butthe 5-iodo isatoic anhydride is preferred (2, R^(a) =I). The β-alanineester 3 may also be substituted or unsubstituted as the free amine or,more conveniently, as its salt (e.g. HCl). For example, the reaction maybe carried out with β-alanine ethyl ester hydrochloride, ethyl3-phenyl-3-aminopropionate p-tosylate, aspartyl-valine dibenzyl esterhydrochloride, or the like. Generally, the reaction is conducted in adry polar aprotic solvent, such as dimethylformamide or the like, in thepresence of an equimolar amount, or up to 30% excess, of a tertiaryamine as the organic base, e.g. triethylamine. Alternatively, thereaction may be catalysed by dimethylaminopyridine (Venuti, M. C. J.C.S.Chem Comm. 1982, 266). The reaction requires between about 0.5 to 4hours at temperatures between about room temperature and 100° C.Preferably, the reaction is conducted at 50° C. for about 2 hours indimethylformamide as the solvent.

The products are isolated and purified by conventional methods,typically by solvent extraction into a compatible solvent. The productmay be further purified by column chromatography or other appropriatemethods.

If the anilino nitrogen in N-(2-aminobenzoyl)-β-alanine esters 6a isunsubstituted such that R=H, this position can be alkylated by allowing6b (R=H) to react with a molar amount, but up to 50% excess, of an alkylhalide to produce 6 (R≠H). Generally, the reaction can be accomplishedin a polar aprotic solvent, in the presence of a molar amount, or up to50% excess, of an organic base. Preferably, the reaction will beconducted in dimethylformamide as solvent and 2,6-lutidine as theorganic base. The reaction is allowed to proceed at temperatures betweenabout room temperature to 200° C. for about 0.5 hours to 2 days.Preferably, the reaction will be run at 80° C. for 16 hours. Theproducts are isolated and purified by conventional methods, typically bysolvent extraction into a compatible solvent. The product may be furtherpurified by column chromatography or other appropriate methods.

Alternatively, 6 (R≠H) may be prepared by allowing 6a to react with analdehyde or ketone, under dehydrating conditions, in the presence of acatalytic amount of acid followed by reduction with a trialkylsilane anda strong acid. Generally, the first of these reactions can beaccomplished in a non-polar aprotic solvent, such as toluene, and anorganic acid, such as p-toluenesulphonic acid at temperatures between80°-160° C. for times between 1 to 60 mins. Preferably, the reactionwill be conducted at reflux for 10 mins. The product may be isolated bycrystallization or carried on to reduction without further purification.Reduction can be achieved by the addition of an excess oftrialkylsilane, such as triethylsilane, in the presence of an excess ofa strong acid, such as trifluoroacetic acid, at temperatures between-30° to 30° C. for times between 0.5 to 48 hours with a non-reactiveorganic solvent, such as dichloromethane. Preferably, reduction is runat 0° C. for 2 hours with dichloromethane as a co-solvent. The productsare isolated and purified by conventional methods, typically bycrystallization from suitable solvents. The product may be otherwisepurified by solvent extraction into a compatible solvent followed bycolumn chromatography or other appropriate methods.

Conversion of N-(2-aminobenzoyl)-β-alanine esters 6 to thebenzodiazepinedione 1 (R≠H) involves first the acylation of the anilinonitrogen, followed by a base promoted ring formation. The acylationreaction can be achieved by either reaction of 6 with an α-haloacylhalide in the presence of an equimolar amount, or up to 30% excess, ofan organic base, such as triethylamine, or with an α-haloacid in thepresence of an amide coupling reagent, such as dicyclohexylcarbodiimide.Acylation of 6 with an a-haloacyl halide may also be conducted in theabsence of an organic base and can be run with water in a biphasicreaction system. Generally, these reactions are conducted in apre-dried, non-reactive organic solvent, such as methylene chloride,diethyl ether, or tetrahydrofuran under a dry, inert atmosphere, such asnitrogen. Preferably, acylation with an α-halo acylhalide will be run inmethylene chloride, whereas acylation with an α-halo-acid will be run intetrahydrofuran. The reactions are allowed to run at temperaturesbetween about 0° C. to room temperature for times between about 0.5 to24 hours. Preferably, the reactions will be allowed to run for 2 hoursat room temperature. The products are isolated and purified byconventional methods, typically by solvent extraction into a compatiblesolvent. Generally, further purification of the acylated products 7 isnot required.

Cyclization of the acylated N-(2-acylaminobenzoyl)-β-alanine esters 7may be achieved by reaction with a base such as an alkali metalalkoxide, hydride, or carbonate in a polar solvent at temperaturesbetween about 0° and 100° C. for about 0.5 to 2 hours. For example, asolution of the N-(2-aminobenzoyl)-β-alanine ester 7 is commonly addedover a period of approximately 15 to 60 minutes to a slurry of an alkalimetal hydride in an appropriate solvent, cooled to 0° C. ##STR27## It ispreferable that the solvent will be a polar aprotic solvent such asdimethylfomamide and the alkali metal hydride be sodium hydride orcalcium carbonate. Once the addition is complete, the reaction mixtureis generally allowed to warm to room temperature and run for anadditional 60 to 105 minutes after which the reaction is neutralized bythe addition of a solution of an acid, such as 10% citric acid or thelike, and the solvent evaporated. The product is then isolated bysolvent extraction and further purified by column chromatography.

In Scheme 2, the substituted N-carboxymethyl β-alanine ester 5 are alsoknown in the art and may be prepared in two steps by first reaction ofan acrylate ester and α-amino acid ester to give 8, followed byselective conversion of the glycine ester group to its correspondingacid. For example, allowing glycine benzyl ester to react with ethylacrylate in an alcoholic solvent such as methanol for about 1 day yieldsN-(carboxymethyl benzyl ester)-β-alanine ethyl ester. Removal of thebenzyl ester by hydrogenation in the presence of a catalytic amount 10%palladium on carbon provides N-carboxymethyl-β-alanine ester 5 (M'=H,R^(b) =ethyl).

Preparation of the benzodiazepinedione 1 (R=H) may be accomplished byallowing 5 to react with 2 (R=H). The reaction can be conducted ineither a ##STR28## polar aprotic solvent, such as dimethyl sulfoxide, orweak organic base, such as pyridine, at temperatures of 100°-200° C. forabout 2-86 hours. Preferably, the reaction will be run in pyridine atrefluxing temperature for about 24 hours. The product is then isolatedby dilution with an appropriate organic solvent, such as ethyl acetate,and washed with aqueous acid, such as 10% citric acid, and aqueous base,such as saturated sodium bicarbonate. The products can be furtherpurified by column chromatography or crystallization from an appropriateorganic solvent to provide the compounds 1 (R=H).

Reaction Scheme 3 outlines the preparation of the compounds of thepresent invention from compound 9 [1 (R^(a) =I)].

Conversion of the compounds having the structural formula 9 to compoundshaving the structural formula 10, provides those compounds classified inGroups 1 and 2. This may be accomplished by allowing 9 to react with analkyne 11 in the presence of a palladium (II) salt, a copper (I) salt,and an organic base. Preferably, the alkyne 11 is substituted in a waysuch that the Y group can be synthetically converted to the positivelycharged Q group of structural Formula I. More preferably, the Y group isa protected form of the positively charged Q group of structural FormulaI. For example, the alkyne may be a N-Boc-amino alkyne, a benzo oralkylnitrile alkyne, a nitrobenzo alkyne, or the like. L' is L less thefunctional groups shown below in scheme 3.

Generally, the reaction is allowed to run in a dry organic polar aproticsolvent, such as ethyl acetate or the like, to the exclusion of oxygenat temperatures between about room temperature and 180° C. for timesbetween about 2 and 48 hours. Preferably, the reaction will run with acatalytic amount of palladium(II) salt at 10 molar percent and cupric(I)salt at 5 molar percent. A 2 fold excess of the alkyne 11 and a 5 foldexcess of a tertiary amine as the organic base, such as triethylamine orthe like, is preferred. For example, a mixture of the iodo arene 9, a 2fold excess of the alkyne 11, 10 molar percent ofbis(triphenylphosphine)palladium dichloride, 5 molar percent cupriciodide, 5 fold excess of triethylamine, and ethyl acetate under a dry,inert atmosphere, such as nitrogen, is allowed run for about 2 hours.The product can be isolated by solvent extraction in to a suitableorganic solvent, such as ethyl acetate, and washed with a solution of10% ethylenediaminetetraacetic acid and the solvent evaporated. Theproducts may be further purified by column chromatography.

Preparation of the compounds classified in Groups 3 and 4 may beachieved by reduction of the alkyne moiety in compounds of the generalformula 10 to yield the saturated compounds 12 by allowing the alkyne tostir under an atmosphere of hydrogen in the presence of a small amountof palladium on carbon. Typically, the reaction is run in an inertsolvent, such as ethyl acetate, with a 5-10 molar percent by weight of10% palladium on carbon at temperatures between about room temperatureand 50° C. for times between about 15-240 minutes. Preferably, thereaction is carried out at room temperature for 1 hour. The products areisolated by filtration of the mixture through a filter agent, such asCelite®, and evaporation of solvent. ##STR29##

Conversion of the compounds of the general formula 10 or 12 in which Yis a N-(tert-butoxycarbonyl) amino protected moiety (N-BOC) to the aminoesters 13 can be accomplished by allowing the material to react with astrong acid. Generally, the reaction is carried out by mixing the N-BOCamino ester with a large excess of concentrated solution of a strongacid, such as hydrogen chloride, dissolved in an appropriate inertsolvent, such as ethyl acetate. The reaction can be conducted at atemperature between about minus 30° C. and room temperature for about0.5 to 24 hours. The reaction can be run in the presence of a molaramount of trialkylsilane, such as triethylsilane or the like.Preferably, the reaction will be carried out at room temperature for 2hours with a molar equivalent of triethylsilane in ethyl acetate. Thesolvent is evaporated and the products can be further purified byhigh-pressure liquid chromatography using a reverse phase column.

Conversion of the compounds of the general formula 10 or 12 in which theY functional group is an arylnitrile to the amino esters 13 can beachieved by allowing the arylnitriles 10 or 12 to react with dicobaltoctacarbonyl in the presence of trimethylsilane. The reduction of abenzonitrile to a benzylamine is a known reaction (Murai, T.; Sakane,T.; Kato, S. Tetrahedron Lett. 1985, 26, 5145-5148) and is generallycarried out in an inert solvent, such as toluene or the like, at 60° C.for 20 hours with an 8 molar percent of dicobalt octacarbonyl and a 10fold excess of trimethylsilane. The solvent is evaporated and theresulting material diluted with methanol and allowed to react with a 5fold excess of potassium fluoride. The products are then isolated bysolvent extraction and further purified high-pressure liquidchromatography using a reverse phase column.

Conversion of the compounds of the general formula 10 or 12 in which theY functional group is a nitroarene, to the amino ester 13 can beexecuted by a selective reduction (Bellamy, F. D.; Ou, K. TetrahedronLett. 1984, 25, 839-842). The reaction is generally run with a fivemolar excess of stannous chloride dihydrate in either ethyl acetate orethanol as the solvent at temperatures between about 50° and 100° C. fortimes between about 15-120 minutes under an inert atmosphere, such asnitrogen. Preferably, the reaction is carried out at 70° C. in ethanolfor approximately 30 minutes. The products are then isolated by solventextraction and further purified by high-pressure liquid chromatographyusing a reverse phase column.

Conversion of the amino esters to their corresponding amino acids of thestructural formula I involves saponification using well known conditionsand reagents. For example, an aqueous solution of a strong alkali metalbase, such as sodium hydroxide, lithium hydroxide or the like, is addedto an alcoholic solution of the ester. Alcohols which may be used as thesolvent for this reaction may include, for example, methanol, ethanol,and isopropanol, but, methanol is preferred. The preferred base issodium hydroxide at a concentration between about 1 to 6N, through 2N ispreferred. The reaction may be conducted at a temperature between about0° to 50° C. for times between about 10 to 60 minutes. Preferably, thereaction is carried out at room temperature for 30 minutes after whichthe reaction is neutralized with a concentrated solution of a strongacid, such as hydrochloric acid or the like, and the solvent evaporated.The products are isolated by high-pressure liquid chromatography using areverse phase column.

The conversion of the amino acids to their corresponding guanidino acidsof the structural formula I is a known reaction (Kim, K. Lin, Y.-L.;Mosher, H. S. Tetrahedron Lett. 1988, 3183-3186). The reaction can beaccomplished by allowing the amino acid to react withaminoiminomethanesulfonic acid. Generally, the reaction can be conductedwith a equimolar to a 10 fold molar excess of aminoiminomethanesulfonicacid at temperatures between 0° to 50° C. for times between about 15 to120 minutes in a polar protic solvent, such as methanol, water or thelike. The solution, prior to the addition of aminoiminomethanesulfonicacid, may be made neutral or basic by the addition of weak base, such asan alkali metal carbonate. Preferably, for alkyl amines the amino acidwill be allowed to react with a 5 fold excess aminoiminomethanesulfonicacid at room temperature for 30 minutes with 5% potassium bicarbonate inwater as the reaction medium, whereas for aryl amines the amino acidwill be allowed to react with an equimolar amount ofaminoiminomethanesulfonic acid at room temperature for 1 hour inmethanol. Generally, the reaction mixture will be made acidic by theaddition of a dilute solution of an acid, such as acetic acid and thesolvent evaporated. The products are isolated by high-pressure liquidchromatography using a reverse phase column.

Preparation of the compounds classified as Groups 4-11 may also beprepared from the key intermediate 9. Conversion of the iodoarene 9 to asynthetic precursors of those compounds found in Groups 5-11 namelycompounds 15-18, may be accomplished by a multistep reaction sequence(Scheme 4). First, the iodoarene is carbonylated in an alcoholic solvent(R'OH) under a carbon monoxide atmosphere utilizing a palladium (0)catalyst. The alcoholic solvent (R'OH) must be chosen so as to allow forthe selective removal of the R' group of the diester 14. For example,when R'═CH₃ and R^(b) =tert-butyl, the alcoholic solvent is methanol,and this methyl ester functionality in 14 can be removed by mild basichydrolysis to afford acid 15. The treatment of 15 with a molarequivalent of diphenylphosphoryl azide and a molar equivalent of atertiary amine such as triethylamine at room temperature in a non-proticsolvent such as dichloromethane affords the isocyanate 16. This may behydrolyzed to the amine 17 by the addition of water to a solution of 16in tetrahydrofuran at room temperature. Finally, conversion of theaniline 17 to its corresponding diazonium salt by treatment with nitrousacid and subsequent heating of the diazonium salt in the presence ofwater produces the phenol 18. ##STR30##

Schemes 5 and 6 depict methods that may be used to introduce the linkinggroups of compounds classified as Groups 4-11 onto thebenzodiazepinedione nucleus. For example, preparation of the biaryladducts 19, precursors of Group 5 type compounds, may be accomplished byallowing 9 to react with substituted aryl molecules 20, where Y and L'are defined as above, in the presence of palladium (0). Allowing thecarboxylic acid 15 to react with an amine 21 or alcohol 22 in thepresence of a dehydrating reagent, such as dicyclohexycarbodiimide (DCC)or the like, will yield the amide 23 and ester 24, forerunners of Group10 and 11 type compounds, respectively. Similarly, 25 can be preparedfrom the aniline 17 by reaction with a carboxylic acid 26 in thepresence of a coupling reagent, such as DCC or the like. Compounds ofthe general formula 25 are precursors of Group 5 type compounds.##STR31##

Conversion of aniline 17 into its corresponding urea 27 or carbamate 28(Scheme 6) may be accomplished by reaction of the isocyanate 16 in thepresence of an amine 21 or alcohol 22, respectively. Treatment of thephenol 18 with phosgene and an amine 21 or alcohol 22 yields thecarbamate 29 and carbonate 30, respectively. Reaction of asulfonylhalide 32 with either the aniline 17 or phenol 18 would producethe corresponding sulfonamide 33 and sufinyl ester 34, respectively.Allowing the phenol 18 to react with an alcohol 22 in the presence ofdiethylazodicarboxylate and triphenylphophine will furnish 31, aprecursor to Group 12 type compounds. The product 27 is a syntheticprecursor to those compounds classified as Group 7, product 28 is aforerunner to Group 6 type compounds, product 29 will give rise to Group8 type compounds, whereas, product 30 is a precursor to Group 9 typecompounds. Products 33 and 34 are precursors to Group 15 and 16,respectively. ##STR32##

Scheme 7 depict methods that may be used in the preparation of thecompounds classified as Groups 13, 14, 17 and 18. Diazotization of theaniline 17, by the reaction of 17 with nitrous acid, followed bytreatment with sulfur dioxide in the presence of cupric chloride(Gilbert, Synthesis, 1969, 1-10) yields the sulfonyl chloride 35.Reaction of 35 with either the amine 21 or the alcohol 22 will providethe synthetic precursor to Groups 13 and 14, respectively, namely, thesuphonamide 36 and sulfinyl ester 37. The diazonium salt prepared bydiazotization of 17 when allowed to react with oximes in the presence ofcopper sulphate and sodium sufite will give the corresponding oxime 38,which can be readily hydrolyzed to yield the aryl ketone 39 (Beech, J.Chem. Soc, 1954, 1297). Clemmensen reduction of the ketone 39 using zincamalgam and aqueous hydrogen chloride gives rise to the benzyl adduct 40(Vedejs, Org. React. 1975, 22, 401). The products 39 and 40 areprecursors to the compounds classified as Groups 17 and 18,respectively. ##STR33##

Each of the protected precursors 19, 23, 24, 25, 27, 28, 29, 30, 31, 33,34, 36, 37, 39, and 40 may be treated in a similar way as describedabove for compounds 10 and 12 (Scheme 3) to prepare the compoundsencompassed by this invention.

3. Other "6-7" Fused Ring Systems

Other "6-7" fused ring systems where each T, U, or G of formula I isindependently selected from NH, N, NR, C═X, CR₂, CHR, CH₂, CR, CH, O, S,SO, or SO₂ can be prepared by methods known in the art. To provideguidance, however, specific representative synthetic routes are providedin scheme 8. It will be understood that other synthetic routes may bepreferred when specific substituents or T-U-G are targeted. ##STR34##

Starting reagents imployed in scheme 8 are either commercially availableor readily synthesized by known procedures.

4. Isomeric Products

In products of Formula I carbon atoms bonded to four nonidenticalsubstituents are asymmetric. Accordingly, the compounds may exist asdiastereoisomers, enantiomers or mixtures thereof. The synthesesdescribed above may employ racemates, enantiomers or diastereomers asstarting materials or intermediates. Diastereomeric products resultingfrom such syntheses may be separated by chromatographic orcrystallization methods. Likewise, enantiomeric product mixtures may beseparated using the same techniques or by other methods known in theart. Each of the asymmetric carbon atoms, when present in compounds ofFormula I, may be in one of two configurations (R or S) and both arewithin the scope of the present invention.

E. Pharmaceutical Compositions

The compounds described in this invention may be isolated as the freeacid or base or converted to salts of various inorganic and organicacids and bases. Such salts are within the scope of this invention.Examples of such salts include ammonium, metal salts like sodium,potassium, calcium and magnesium; salts with organic bases likedicyclohexylamine, N-methyl-D-glucamine and the like; and salts withamino acids like arginine or lysine. Salts with inorganic and organicacids may be likewise prepared, for example, using hydrochloric,hydrobromic, sulfuric, phosphoric, trifluoroacetic, methanesulfonic,malic, maleic, fumaric and the like. Non-toxic and physiologicallycompatible salts are particularly useful although other less desirablesalts may have use in the processes of isolation and purification.

A number of methods are useful for the preparation of the saltsdescribed above and are known to those skilled in the art. For example,reaction of the free acid or free base form of a compound of Formula Iwith one or more molar equivalents of the desired acid or base in asolvent or solvent mixture in which the salt is insoluble; or in asolvent like water after which the solvent is removed by evaporation,distillation or freeze drying. Alternatively, the free acid or base formof the product may be passed over an ion exchange resin to form thedesired salt or one salt form of the product may be converted to anotherusing the same general process.

In the management of thromboembolic disorders the compounds of thisinvention may be utilized in compositions such as tablets, capsules orelixirs for oral administration; suppositories for rectaladministration; sterile solutions or suspensions for injectableadministration, and the like. Animals in need of treatment usingcompounds of this invention can be administered dosages that willprovide optimal efficacy. The dose and method of administration willvary from animal to animal and be dependent upon such factors as weight,diet, concurrent medication and other factors which those skilled in themedical arts will recognize.

Dosage formulations of the nonpeptidyl inhibitors of the presentinvention are prepared for storage or administration by mixing theinhibitor having the desired degree of purity with physiologicallyacceptable carriers, excipients, or stabilizers. Such materials arenon-toxic to the recipients at the dosages and concentrations employed,and include buffers such as phosphate, citrate, acetate and otherorganic acid salts; antioxidants such as ascorbic acid; low molecularweight (less than about ten residues) peptides such as polyarginine,proteins, such as serum albumin, gelatin, or immunoglobulins;hydrophilic polymers such as polyvinylpyrrolidinone; amino acids such asglycine, glutamic acid, aspartic acid, or arginine; monosaccharides,disaccharides, and other carbohydrates including cellulose or itsderivatives, glucose, mannose, or dextrins; chelating agents such asEDTA; sugar alcohols such as mannitol or sorbitol; counterions such assodium and/or nonionic surfactants such as Tween, Pluronics orpolyethyleneglycol.

Dosage formulations of the nonpeptidyl inhibitors of the presentinvention to be used for therapeutic administration must be sterile.Sterility is readily accomplished by filtration through sterilefiltration membranes such as 0.2 micron membranes. Nonpeptidyl inhibitorformulations ordinarily will be stored in lyophilized form or as anaqueous solution. The pH of the cyclic inhibitor preparations typicallywill be between 3 and 11, more preferably from 5 to 9 and mostpreferably from 7 to 8. It will be understood that use of certain of theforegoing excipients, carriers, or stabilizers will result in theformation of cyclic polypeptide salts. While the preferred route ofadministration is by hypodermic injection needle, other methods ofadministration are also anticipated such as suppositories, aerosols,oral dosage formulations and topical formulations such as ointments,drops and dermal patches.

Therapeutic nonpeptidyl inhibitor formulations generally are paced intoa container having a sterile access port, for example, an intravenoussolution bag or vial having a stopper pierceable by hypodermic injectionneedle.

Therapeutically effective dosages may be determined by either in vitroor in vivo methods. For each particular nonpeptidyl inhibitor of thepresent invention, individual determinations may be made to determinethe optimal dosage required. The range of therapeutically effectivedosages will naturally be influenced by the route of administration. Forinjection by hypodermic needle it may be assumed the dosage is deliveredinto the body's fluids. For other routes of administration, theabsorption efficiency must be individually determined for each inhibitorby methods well known in pharmacology.

The range of therapeutic dosages is from about 0.001 nM to 1.0 mM, morepreferably from 0.1 nM to 100 mM, and most preferably from 1.0 nM to 50mM.

Typical formulation of compounds of Formula I as pharmaceuticalcompositions are discussed below.

About 0.5 to 500 mg of a compound or mixture of compounds of Formula I,as the free acid or base form or as a pharmaceutically acceptable salt,is compounded with a physiologically acceptable vehicle, carrier,excipient, binder, preservative, stabilizer, flavor, etc., as called forby accepted pharmaceutical practice. The amount of active ingredient inthese compositions is such that a suitable dosage in the range indicatedis obtained.

Typical adjuvants which may be incorporated into tablets, capsules andthe like are a binder such as acacia, corn starch or gelatin; anexcipient such as microcrystalline cellulose; a disintegrating agentlike corn starch or alginic acid; a lubricant such as magnesiumstearate; a sweetening agent such as sucrose or lactose; a flavoringagent such as peppermint, wintergreen or cherry. When a dosage form is acapsule, in addition to the above materials it may also contain a liquidcarrier such as a fatty oil. Other materials of various types may beused as coatings or as modifiers of the physical form of the dosageunit. A syrup or elixir may contain the active compound, a sweetner suchas sucrose, preservatives like propyl paraben, a coloring agent and aflavoring agent such as cherry. Sterile compositions for injection canbe formulated according to conventional pharmaceutical practice. Forexample, dissolution or suspension of the active compound in a vehiclesuch as water or naturally occurring vegetable oil like sesame, peanut,or cottonseed oil or a synthetic fatty vehicle like ethyl oleate or thelike may be desired. Buffers, preservatives, antioxidants and the likecan be incorporated according to accepted pharmaceutical practice.

F. Platelet Inhibition Assays

Evaluation of the Formula I inhibitors of the fibrinogen-plateletinteraction is guided by in vitro receptor binding assays and in vitroplatelet aggregation inhibition assays.

In-vitro biological activity of the compounds of Formula I are monitoredusing a modified fibrinogen-GPIIbIIIa ELISA based on the method ofNachman and Leung (J. Clin. Invest. 69:263-269 (1982) which measures theinhibition of fibrinogen binding to purified human platelet GPIIbIIIareceptor. Human fibrinogen is prepared by the method of Lipinska, et al.(J. Lab. Clin. Med. 84:509-516 (1974)). Platelet GPII_(b) III_(a) isprepared by the method of Fitzgerald, et al., Anal. Biochem.,151:169-177(1985).

Briefly, microtiter plates are coated with fibrinogen (10 mg/ml) andthen blocked with TACTS buffer containing 0.5% bovine serum albumin(BSA). (TACTS buffer contains 20 mM Tris.HCl, pH 7.5, 0.02% sodiumazide, 2 mM calcium chloride, 0.05% Tween 20, 150 mM sodium chloride.)The plate is washed with phosphate buffered saline (PBS) containing0.01% Tween 20 and the sample to be determined added, followed byaddition of solubilized GP IIbIIIa receptor (40 mg/ml) in TACTS, 0.5%BSA. After incubation, the plate is washed and 1 mg/ml of murineanti-platelet monoclonal antibody AP3 (Newman et al., Blood 65:227-232(1985)) is added. After another wash a goat anti-mouse IgG conjugated tohorseradish peroxidase is added. A final wash is performed anddeveloping reagent buffer (10 mg o-phenylenediamine dihydrochloride,0.0212% hydrogen peroxide, 0.22 mM citrate, 50 mM phosphate, pH 5.0) isadded and then incubated until color develops. The reaction is stoppedwith 1N sulfuric acid and the absorbance at 492 nm is recorded.

In addition to the GPII_(b) III_(a) ELISA assay, platelet aggregationassays may be performed in human platelet rich plasma (PRP). Fiftymilliliters of whole human blood (9 parts) is drawn on 3.6% sodiumcitrate (1 part) from a donor who has not taken aspirin or relatedmedications for at least two weeks. The blood is centrifuged at 160×gfor 10 min at 22° C. and then allowed to stand for 5 min after which thePRP is decanted. Platelet poor plasma (PPP) is isolated from theremaining blood after centrifugation at 2000×g for 25 min. The plateletcount of the PRP is adjusted to ca. 300,000 per microliter with PPP.

A 225 mL aliquot of PRP plus 25 mL of either a dilution of the testsample or a control (PBS) is incubated for 5 min in a Chrono-log WholeBlood Aggregometer at 25° C. An aggregating agent (collagen, 1 mg/ml;U46619, 100 ng/ml; or ADP, 8 mM) is added and the platelet aggregationrecorded.

Without further description, it is believed that one of ordinary skillin the art can, using the preceding description and illustrativeexamples, make and utilize the present example to the fullest extent.The following working examples therefore, specifically point outpreferred embodiments of the present invention, and are not to beconstrued as limiting in any way the remainder of the disclosure.

All references cited herein are expressly incorporated by reference.

EXAMPLES EXAMPLE 1 ##STR35##1-methyl-4-(2-carboxyethyl)-7-(5-amino-1-pentynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate.

a) To a mechanically stirred solution of 26.3 grams of 5-iodo-2-aminobenzoic acid (0.1 mol), 10.6 grams of sodium carbonate (0.1 mol), and250 mL water, cooled to 0° C., was slowly added, via an addition funnel,80 mL of a 1.93M solution of phosgene in toluene. After 2 hours, theprecipitated product was isolated by filtration. The solids were washedwith 200 mL water, 300 mL of a 1:1 mixture ethanol and ether, 200 mL ofether, and dried under vacuum to yield 24.3 grams (84%) of 5-iodoisatoicanhydride (264°-268° C., decomposition).

b) a magnetically stirred solution of 5 grams of 5-iodoisatoic anhydride(0.0173 mol), 5.85 grams of β-alanine benzyl ester tosylate (0.0173mol), 35 mL pyridine, and 0.5 of dimethylaminopyridine (0.0041 mol) washeated to 80° C. for 2 hrs. The reaction mixture was allowed to cool toroom temperature and concentrated in vacuo. The resulting residue wasdissolved in 100 mL ethyl acetate and washed 2×50 mL of 10% cupricsulfate, 1×50 mL sat. sodium bicarbonate, 1×50 mL brine, dried oversodium sulfate, filtered and concentrated in vacuo. The product wasfurther purified by column chromatography, using silica gel, elutingwith a 1:1 mixture of ethyl acetate and hexane (TLC, SiO₂, 1:1EtOAc/hexane, R_(f) =0.65, υν positive) to yield 1.85 grams (25%) ofN-(2-amino-5-iodobenzoyl)-β-alanine benzyl ester. ¹ H NMR (CDCl₃, δTMS)7.54 (1H, d, ⁴ J_(HH) =2 Hz, Ar--H, o-CON), 7.42 (1H, dd, ³ J_(HH) =9Hz, ⁴ J_(HH) =2 Hz, Ar--H p-CON), 7.38-7.32 (5H, s, ArH Ph), 6.65 (1H,bt, ³ J_(HH) =6 Hz, CONH), 6.46 (1H, d, ³ J_(HH) =9 Hz, Ar--H m-CON),5.16 (2H, s, OCH₂), 3.68 (2H, q, ³ J_(HH) 6 Hz, NCH₂), 2.69 (2H, t, ³J_(HH) =6 Hz, CH₂ CO₂). ¹³ C NMR (CDCl₃, δTMS) 172.4, 167.8, 148.6,140.6, 135.6, 135.5, 128.7, 128.4, 128.3, 119.3, 118.1, 76.3, 66.7,35.2, 34.0.

Using the above procedure, but substituting the appropriate3-aminoproprionate alkyl ester for β-alanine ethyl ester andN-substituted-5-iodo-isatoic anhydride for 5-iodoisatoic anhydride theremay be prepared, for example, the following compounds:

ethyl N-(2-amino-5-iodobenzoyl)-3-amino-3-methylpropanoate,

ethyl N-(2-amino-5-iodobenzoyl)-3-amino-3-phenylpropanoate,

ethylN-(2-amino-5-iodobenzoyl)-3-amino-3-(3-(methoxycarbonyl)phenyl)propanoate,

t-butyl N-[N-(2-amino-5-iodobenzoyl)-L-(b-benzyl)-aspartinate,

ethyl N-[N-(2-amino-5-iodobenzoyl)-L-aspartyl-(β-benzylester)]-glycinate,

ethyl N-[N-(2-amino-5-iodobenzoyl)-Laspartyl-(β-benzyl ester)]-valinate,

ethyl N-[N-(2-amino-5-iodobenzoyl)-L-aspartyl-(β-benzylester)]phenylalaninate,

ethyl N-(2-(N-methyl)-amino-5-iodobenzoyl)-3-amino-3-methylpropanoate,

ethyl N-(2-(N-methyl)-amino-5-iodobenzoyl)-3-amino-3-phenylpropanoate,

ethylN-(2-(N-methyl)-amino-5-iodobenzoyl)-3-amino-3-(3-(methoxycarbonyl)phenyl)propanoate,

t-butylN-[N-[2-(N-methyl)-amino-5-iodobenzoyl]-(±)-(β-benzyl)-aspartinate

ethyl N-[N-(2-(N-methyl)-amino-5-iodobenzoyl)-(±)-aspartyl-(β-benzylester)]glycinate,

ethyl N-[N-(2-(N-methyl)-amino-5-iodobenzoyl)-(±)-aspartly-(β-benzylester)]valinate,

ethyl N-[N-(2-(N-methyl)-amino-5-iodobenzoyl)-(±)-aspartyl-(β-benzylester)]phenylalaninate,

ethyl N-(2-(N-phenyl)-amino-5-iodobenzoyl)-3-amino-3-methylpropanoate,

ethyl N-(2-(N-phenyl)-amino-5-iodobenzoyl)-3-amino-3-phenylpropanoate,

ethylN-(2-(N-phenyl)-amino-5-iodobenzoyl)-3-amino-3-]3-(methoxycarbonyl)phenyl]propanoate,

t-butylN-[N-[2-(N-phenyl)-amino-5-iodobenzoyl]-(±)-(β-benzyl)-aspartinate

ethyl N-[N-(2-(N-phenyl)-amino-5-iodobenzoyl)-(±)-aspartly-(β-benzylester)]glycinate,

ethyl N-[N-(2-(N-phenyl)-amino-5-iodobenzoyl)-(±)-aspartyl-(β-benzylester)]valinate,

ethyl N-[N-(2-(N-phenyl)-amino-5-iodobenzoyl)-(±)-aspartyl-(β-benzylester)]phenylalaninate,

ethyl N-(2-(N-benzyl)-amino-5-iodobenzoyl)-3-amino-3-methylpropanoate,

ethyl N-(2-(N-benzyl)-amino-5-iodobenzoyl)-3-amino-3-phenylpropanoate,

ethylN-(2-(N-benzyl)-amino-5-iodobenzoyl)-3-amino-3-(3-(methoxycarbonyl)phenyl)propanoate,

t-butylN-[N-[2-(N-benzyl)-amino-5-iodobenzoyl]-(±)-(β-benzyl)-aspartinate

ethyl N-[N-(2-(N-benzyl)-amino-5-iodobenzoyl)-(±)-aspartyl-(β-benzylester)]glycinate,

ethyl N-[N-(2-(N-benzyl)-amino-5-iodobenzoyl)-(±)-aspartyl-(β-benzylester)]valinate,

ethyl N-[N-(2-(N-benzyl)-amino-5-iodobenzoyl)-(±)-aspartyl-(β-benzylester)]phenylalaninate,

ethylN-(2-(N-isopropyl)-amino-5-iodobenzoyl)-3-amino-3-methylpropanoate,

ethylN-(2-(N-isopropyl)-amino-5-iodobenzoyl)-3-amino-3-phenylpropanoate,

ethylN-(2-(N-isopropyl)-amino-5-iodobenzoyl)-3-amino-3-(3-(methoxycarbonyl)phenyl)propanoate,

t-butylN-[N-[2-(N-isopropyl)-amino-5-iodobenzoyl)-(±)-aspartyl-(β-benzyl)-aspartinate,

ethyl N-[N-(2-(N-isopropyl)-amino-5-iodobenzoyl)-(±)-aspartyl-(β-benzylester)]-glycinate,

ethyl N-[N-(2-(N-isopropyl)-amino-5-iodobenzoyl)-(±)-aspartyl-(β-benzylester)]-valinate,

ethyl N-[N-(2-(N-isopropyl)-amino-5-iodobenzoyl)-(±)-aspartyl-(β-benzylester)]-phenylalaninate,

c) A magnetically stirred solution of 0.848 gram ofN-(2-amino-5-iodobenzoyl)-β-alanine ethyl ester (2.0 mmol), 0.35 mL2,6-lutidine (3.0 mmol), 0.19 mL methyl iodide (3.0 mmol), and 15 mLdimethylformamide was heated to 50° C. for 15 hours. The reactionmixture was allowed to cool to room temperature and concentrated invacuo. The resulting residue was dissolved in 75 mL ethyl acetate andwashed 1×50 mL 10% citric acid, 1×50 mL sat. sodium bicarbonate, 1×50 mLbrine, dried over magnesium sulfate, filtered and concentrated in vacuo.The resulting oil was further purified by column chromatography, usingsilica gel, eluting with a solvent gradient of 35/65 ethylacetate/hexane to 65/35 ethyl acetate/hexane (TLC, SiO₂, 1:1EtOAc/hexane, R_(f) =0.84, υν positive) to yield 305 mgs (35%) ofN-(2-methylamino-5-iodobenzoyl)-β-alanine benzyl ester. ¹ H NMR (CDCl₃,dTMS) 7.56 (2H, m, Ar--H o,p-CON), 7.43 (1H, bq, ³ J_(HH) =5 Hz, NHMe),7.38-7.32 (5H, s, ArH Ph), 6.62 (1H, bt, ³ J_(HH) =6 Hz, CONH), 6.42(1H, d, ³ J_(HH) =9 Hz, Ar--H m-CON), 5.16 (2 H, s, OCH₂), 3.64 (2H, q,³ J_(HH) =6 Hz, NCH₂), 2.81 (3H, d, ³ J_(HH) =5 Hz, NCH₃), 2.64 (2H, t,³ J_(HH) =6 Hz, CH₂ CO₂). ¹³ C NMR (CDCl₃, δTMS) 172.4, 168.4, 148.8,141.0, 135.5, 128.7, 128.4, 128.3, 117.3, 113.4, 74.1, 66.7, 35.2, 34.0,29.6.

d) To a magnetically stirred solution of 0.305 grms ofN-(2-methylamino-5-iodobenzoyl)-β-alanine benzyl ester (0.69 mmol), 3 mLmethylene chloride, and 0.144 mL triethylamine (1.04 mmol), cooled to-30° C. under an atmosphere of nitrogen was slowly added 0.09 mL ofα-bromoacetylbromide (1.04 mmol) as a solution in 2 mL methylenechloride. The reaction mixture was allowed to warm to room temperatureand stir for 2 hours. The mixture was diluted with 40 mL methylenechloride and washed with 1×50 10% citric acid, 1×50 sat. sodiumbicarbonate, dried over sodium sulfate, filtered and concentrated invacuo. The resulting residue was dissolved in 3 mL dimethylformamide andadded, via an addition funnel, to a slurry of 25 mgs sodium hydride(1.04 mmol) in 2 mL dimethylformamide that was cooled to 0° C. After 2hours, the mixture was poured over 50 mL of an ice cooled solution of 10% citric acid and extracted with 3×40 mL ethyl acetate. The combinedorganic layers were washed with 1×50 mL sat. sodium bicarbonate, driedover magnesium sulfate, and concentrated in vacuo. The resulting residuewas further purified by column chromatography, using silica gel, elutingwith a solvent gradient of 40:60 ethyl acetate/hexane to 70:30 ethylacetate/hexane to yield 0.16 gms (49%) of1-methyl-4-(2-carboxyethyl)-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionebenzyl ester (TLC, SiO₂, 1:1 ethyl acetate/hexane, R_(f) =0.48, υνpositive). ¹ H NMR (CDCl₃, dTMS) 8.15 (1H, d, ⁴ J_(HH) =2 Hz, Ar--Ho-CON), 7.78 (1H, dd, ⁴ J_(HH) =2 Hz, ³ J_(HH) =9 Hz, Ar--H p-CON), 6.90(1H, d, ³ J_(HH) =9 Hz, Ar--H m-CON), 5.1 (2H, s, OCH₂), 3.92 (1H, d, ²J_(HH) =14 Hz, COCHHN), 3.90 (2H, t, ³ J_(HH) =8 Hz, NCH₂), 3.82 (1H, d,² J_(HH) =14 Hz, COCHHN) 3.27 (3H, s, NCH₃), 2.82 (1H, dt, ² J_(HH) =19Hz, ³ J_(HH) =9 Hz, CHHCO₂), 2.68 (1H, dt, ² J_(HH) =19 Hz, ³ J_(HH) =9Hz, CHHCO₂).

Using the above procedure, but substituting the appropriateN-(2-amino-5-iodobenzoyl)-β-alanine alkyl ester forN-(2-methylamino-5-iodobenzoyl)-β-alanine benzyl ester andα-substituted-α-halo acetyl halide for α-bromo acetyl bromide there maybe prepared, for example, the following compounds:

1-methyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-methyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxphenylalanyl-4-benzyloxy)succinyl)]-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-benzyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-benzyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-isopropyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-isopropyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-methyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-methyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-iodo-3,4-dihydro-3-phenyl-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1,3-diphenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1,3-diphenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-benzyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-benzyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-isopropyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-isopropyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

e) To a magnetically stirred solution of 9.13 grams hex-5-ynoic acid(0.081 mol), 7.12 mL triethylamine (0.051 mol), 30 mL tert-butanol, wasadded 17.7 mL diphenylphosphoryl azide (0.082 mol) and the mixtureheated to reflux for 3 hours. The reaction mixture was allowed to coolto room temperature and poured over a biphasic mixture of 200 mL waterand 200 mL ether. The layers were separated and the organic layer waswashed 1×50 mL 5% ethylenediaminetetraacetic acid disodium salt, 1×50 mL10% sodium bicarbonate, 1×50 mL brine, dried over magnesium sulfate andactivated carbon, filtered and concentrated in vacuo. The resultingresidue was further purified by column chromatography, using silica gel,eluting with 1:1 ether/hexane (TLC, SiO₂, 1:3 ethyl acetate/hexane,R_(f) =0.18, ninhydrin char) to yield 3.8 grams (25%)N-boc-5-amino-1-pentyne. ¹ H NMR (CDCl₃, δTMS) 4.65 (1H, bs, NH), 3.22(2H, q, ³ J_(HH) =6 Hz, NCH₂), 2.23 (2H, dt, ³ J_(HH) =6 Hz, ⁴ J_(HH) =3Hz, CH₂ C∫C), 1.98 (1H, t, ⁴ J_(HH) =3 Hz, C∫CH), 1.73 (2H, p, ³ J_(HH)=6 Hz, CH₂), 1.42 (9H, s, t-Bu)

f) To a magnetically stirred solution of 160 mgs1-methyl-2-(carboxyethyl)-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionebenzyl ester (0.335 mmol) in 5 mL ethyl acetate, degassed of oxygen,under an atmosphere of nitrogen was added 123 mgsN-boc-5-amino-1-pentyne (0.67 mmol), 10 mgs bistriphenylphosphinepalladium dichloride (0.014 mmol), 5 mgs cuprous iodide (0.026 mmol) and0.233 mL triethylamine (1.675 mmol). After 2 hours, the reaction mixturewas diluted with 50 mL ethyl acetate and washed 2×50 mL 10% citric acid,2×50 mL sat. sodium bicarbonate, dried over magnesium sulfate, filtered,and concentrated in vacuo. The resulting residue was further purified bycolumn chromatography, using silica gel, eluting with a solvent gradientof 50:50 ethyl acetate/hexane to 75:25 ethyl acetate/hexane (TLC, SiO₂,1:1 ethyl acetate/hexane, R_(f) =0.39, υν positive) to yield 90 mgs(50%)1-methyl-4-(2-carboxyethyl)-7-(N-boc-5-amino-1-pentynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester. ¹ H NMR (CDCl₃, δTMS) 7.85 (1H, d, ⁴ J_(HH) =2 Hz, Ar-Ho-CON), 7.48 (1H, dd, ⁴ J_(HH) =2 Hz, ³ J_(HH) =8 Hz, Ar-H p-CON), 7.32(5H, s, Ph), 7.06 (1H, d, ³ J_(HH) =8 Hz, Ar-H m-CON), 5.10 (2H, s,OCH₂), 4.67 (1H, bs, NH), 3.95 (1H, d, ² J_(HH) =15 Hz, NCHHCO), 3.91(2H, t, ³ J_(HH) =7 Hz, NCH₂), 3.81 (1H, d, ² J_(HH) =15 Hz, NCHHCO),3.29 (3H, s, NCH₃), 3.26 (2H, q, ³ J_(HH) =7 Hz, BocNHCH₂), 2.82 (1H,dt, ² J_(HH) =16 Hz, ³ J_(HH) =8 Hz, CHHCO₂), 2.69 (1H, dt, ² J_(HH) =16Hz, ³ J_(HH) =8 Hz, CHHCO₂), 2.46 (2H, t, ³ J_(HH) =7 Hz, C∫CCH₂), 1.78(2H, p, ³ J_(HH) =7 Hz, CH₂ CH₂ CH₂).

Using the above procedure, but substituting the appropriate7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione for1-methyl-2-(carboxyethyl)-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionebenzyl ester and alkyne for N-boc-5-amino-1-pentyne there may beprepared, for example, the following compounds:

1-methyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-(N-Boc)-amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-methyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-(N-Boc)-amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-(N-Boc)-amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-(N-Boc)-amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxphenylalanyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-benzyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-(N-Boc)-amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-benzyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-(N-Boc)-amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-isopropyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-(N-Boc)-amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-isopropyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-(N-Boc)-amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-methyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-methyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-benzyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-benzyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-isopropyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-isopropyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-methyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-methyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-benzyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-benzyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-isopropyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-isopropyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-methyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-methyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-benzyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-benzyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-isopropyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-isopropyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-methyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-methyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-benzyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-benzyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-isopropyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-isopropyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-methyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-methyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-benzyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-benzyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-isopropyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-isopropyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-methyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-[2-(N-Boc)-aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-methyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione

(±)-1-methyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione

(±)-1-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-benzyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-benzyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione

(±)-1-benzyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-isopropyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-isopropyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-methyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-methyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-benzyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-benzyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-isopropyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-isopropyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione

1-methyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-methyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-benzyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-benzyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-isopropyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-isopropyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-methyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-methyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-benzyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-benzyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-isopropyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-isopropyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-(N-Boc)-amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-(N-Boc)-amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-(N-Boc)-amino-1-pentyne]3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-(N-Boc)-amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-(N-Boc)-amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-(N-Boc)-amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-(N-Boc)-amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-(N-Boc)-amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-(4-nitrophenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione

(±)-1,3-diphenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyn-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodizepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminioethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1(±)-,3-diphenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione

(±)-1,3-diphenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)[-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

g) To a solution of 22 mgs1-methyl-4-(2-carboxyethyl)-7-(N-boc-5-amino-1-pentynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionebenzyl ester (0.0412 mmol) in 0.5 mL ethyl acetate was added 3 mL sat.HCl in ethyl acetate. After 1 hour, the mixture was concentrated invacuo and diluted with 2 mL methanol. To the methanolic solution wasadded 0.5 mL 2N sodium hydroxide. After 1 hour, the reaction wasquenched with 3 mL acetic acid, concentrated in vacuo, diluted with 3 mLwater and purified by high pressure liquid chromatography, using a 1/2"C-18 reverse-phase column, eluting with a solvent gradient of 10:90methanol(0.1% trifluroacetic acid/water (0.1% trifluroacetic acid), time0 to 10 min, to 50:50 methanol(0.1% trifluroacetic acid)/water (0.1%trifluroacetic acid), time 10 min to 40 min, flow=10 ml/min (R_(t) =33.1min, un detection 254 nm) to yield 13 mgs (92%)1-methyl-4-(2-carboxyethyl)-7-(5-amino-1-pentynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate. HRMS (FAB) molecular ion m/z=344.1626 (cald. C₁₈ H₂₂ N₃O₄, 344.1610). ¹ H NMR (D₂ O) 7.63 (1H, d, ⁴ J_(HH), Ar-H o-CON), 7.54(1H, dd, ⁴ J_(HH) =2 Hz, ³ J_(HH) =8 Hz, Ar-H p-CON), 7.20 (1H, d, ³J_(HH) =8 Hz, Ar-H m-CON), 4.05 (1H, d, ² J_(HH) =14 Hz, NCHHCO), 4.0(1H, m, NCHHCH₂), 3.74 (1H, d, ² J_(HH) =14 Hz, NCHHCO), 3.59 (1H, m,NCHHCH₂), 3.20 (3H, s, NCH₃), 3.03 (2H, t, ³ J_(HH) =7 Hz, NCH₂), 2.59(2 H, m, CH₂ CO₂), 2.42 (2H, t, ³ J_(HH) =7 Hz, C∫CCH₂), 1.82 (2H, p, ³J_(HH) =7 Hz, CH₂ CH₂ CH₂).

Using the above procedure, but substituting the appropriate3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione for1-methyl-4-(2-carboxyethyl)-7-(N-boc-5-amino-1-pentynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionebenzyl ester there may be prepared, for example, the followingcompounds:

1-methyl-4-(2-carboxy-1-methylethyl)-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-methyl-4-(2-carboxy-1-phenylethyl)-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-t-butoxy)]-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-glycine)]-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-valine)]-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-phenylalanine)]-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-methylethyl)-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-phenylethyl)-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-glycine)]-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-valine)]-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-methylethyl)-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-phenylethyl)-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-t-butoxy)]-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-glycine)]-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-valine)]-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-phenylalanine)]-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-methylethyl)-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-phenylethyl)-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-t-butoxy)]-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-glycine)]-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-valine)]-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-phenylalanine)]-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-methyl-4-(2-carboxy-1-methylethyl)-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-methyl-4-(2-carboxy-1-phenylethyl)-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-t-butoxy)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-glycine)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-valine)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-phenylalanine)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoracetate,

1-phenyl-4-(2-carboxy-1-methylethyl)-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-phenylethyl)-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-glycine)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-valine)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-methylethyl)-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-phenylethyl)-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-t-butoxy)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-glycine)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-valine)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-phenylalanine)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-methylethyl)-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-phenylethyl)-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-t-butoxy)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-glycine)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-valine)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-phenylalanine)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-methyl-4-(2-carboxy-1-methylethyl)-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-methyl-4-(2-carboxy-1-phenylethyl)-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-t-butoxy)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-glycine)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-valine)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-phenylalanine)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-methylethyl)-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-phenylethyl)-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-glycine)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-valine)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-methylethyl)-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-phenylethyl)-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-t-butoxy)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-glycine)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-valine)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-phenylalanine)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-methylethyl)-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-phenylethyl)-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-t-butoxy)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-glycine)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-valine)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-phenylalanine)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-methyl-4-(2-carboxy-1-methylethyl)-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-methyl-4-(2-carboxy-1-phenylethyl)-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-glycine)]-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-valine)]-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-methylethyl)-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-phenylethyl)-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-glycine)]-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-valine)]-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-methylethyl)-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoracetate,

1-benzyl-4-(2-carboxy-1-phenylethyl)-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-glycine)]-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-valine)]-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-methylethyl)-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-phenylethyl)-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-glycine)]-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-valine)]-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-methyl-4-(2-carboxy-1-methylethyl)-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-methyl-4-(2-carboxy-1-phenylethyl)-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-t-butoxy)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-glycine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-valine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-phenylalanine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-methylethyl)-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-phenylethyl)-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-glycine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-valine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepin-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-methylethyl)-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-phenylethyl)-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-t-butoxy)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-glycine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-valine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-phenylalanine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-methylethyl)-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-phenylethyl)-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-t-butoxy)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-glycine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-valine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-phenylalanine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-methyl-4-(2-carboxy-1-methylethyl)-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-methyl-4-(2-carboxy-1-phenylethyl)-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-t-butoxy)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-glycine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-valine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-phenylalanine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-methylethyl)-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-phenylethyl)-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-glycine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-valine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-methylethyl)-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-benzyl-4-(2-carboxy-1-phenylethyl)-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-t-butoxy)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-glycine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-valine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-phenylalanine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-methylethyl)-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-phenylethyl)-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-t-butoxy)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-glycine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-valine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-phenylalanine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-methylethyl)-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-phenylethyl)-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-t-butoxy)]-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-glycine)]-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-valine)]-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-phenylalanine)]-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-methylethyl)-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-phenylethyl)-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-glycine)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-valine)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-methylethyl)-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-phenylethyl)-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-glycine)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-valine)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-methylethyl)-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-phenylethyl)-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-glycine)]-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-valine)]-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(2-aminoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-methylethyl)-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-phenylethyl)-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-glycine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-valine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[4-(2-amino-6-methylpyrimidine-4yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)]-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-methylethyl)-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-phenylethyl)-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-glycine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-valine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

)±)-1-benzyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate.

EXAMPLE 2 ##STR36##1-methyl-4-(2-carboxyethyl)-7-(5-guanidino-1-pentynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate.

To a magnetically stirred solution of 6 mgs of1-methyl-4-(2-carboxyethyl)-7-(5-amino-1-pentynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate (0.017 mmol) in 1.0 mL 10% potassium bicarbonate wasadded 31.0 mgs of formamidine sulfonic acid (0.25 mmol). After 30minutes, the reaction mixture was quenched with 0.5 mL acetic acid andconcentrated in vacuo. The resulting residue was diluted with 2 mL waterand purified by high pressure liquid chromatography, using a 1/2" C-18reverse-phase column, eluting with a solvent gradient of 10:90 methanol(0.1% trifluroacetic acid)/water (0.1% trifluroacetic acid), time 0 to10 min, to 50:50 methanol (0.1% trifluroacetic acid)/water (0.1%trifluroacetic acid), time 10 min to 40 min, flow=10 ml/min (R_(t) =36.8min, un detection 254 nm) to yield 4.5 mgs (67%)1-methyl-4-(2-carboxyethyl)-7-(5-guanidino-1-pentynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate. HRMS (FAB) molecular ion m/z=386.1823 (cald. C₁₉ H₂₄ N₅O₄, 386.1829). ¹ H NMR (D₂ O) 7.60 (1H, d, ⁴ J_(HH), Ar--H o-CON), 7.51(1H, dd, ⁴ J_(HH) =2 Hz, ³ J_(HH) =8 Hz, Ar--H p-CON), 7.20 (1H, d, ³J_(HH) =8 Hz, Ar--H m-CON), 4.05 (1H, d, ² J_(HH) =14 Hz, NCHHCO), 3.92(1H, m, NCHHCH₂), 3.72 (1H, d, ² J_(HH) =14 Hz, NCHHCO), 3.40 (1H, m,NCHHCH₂), 3.23-3.15 (5H, NCH₃, H₂ NC(=NH₂)NHCH₂), 2.58 (2H, m, CH₂ CO₂),2.38 (2H, t, ³ J_(HH) =7 Hz, C∫CCH₂), 1.76 (2H, p, ³ J_(HH) =7 Hz, CH₂CH₂ CH₂).

Using the above procedure, but substituting the appropriate amino acidfor1-methyl-4-(2-carboxyethyl)-7-(5-amino-1-pentynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate there may be prepared, for example, the followingcompounds:

1-methyl-4-(2-carboxy-1-methylethyl)-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-methyl-4-(2-carboxy-1-phenylethyl)-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-t-butoxy)]-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-glycine)]-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-valine)]-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-phenylalanine)]-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-methylethyl)-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-phenylethyl)-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-glycine)]-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-valine)]-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-methylethyl)-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-phenylethyl)-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-t-butoxy)]-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-glycine)]-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-valine)]-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-phenylalanine)]-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-methylethyl)-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-phenylethyl)-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-t-butoxy)]-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-glycine)]-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-valine)]-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-phenylalanine)]-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-methyl-4-(2-carboxy-1-methylethyl)-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-methyl-4-(2-carboxy-1-phenylethyl)-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-t-butoxy)]-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-glycine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-valine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-phenylalanine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-methylethyl)-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-phenylethyl)-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-glycine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-valine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-phenylalanine)]7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-methylethyl)-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-phenylethyl)-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-t-butoxy)]-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-glycine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-valine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-phenylalanine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-methylethyl)-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-phenylethyl)-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-t-butoxy)]-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-glycine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-valine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-phenylalanine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-methyl-4-(2-carboxy-1-methylethyl)-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-methyl-4-(2-carboxy-1-phenylethyl)-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-t-butoxy)]-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-glycine)]-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-valine)]-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-phenylalanine)]-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-methylethyl)-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-phenylethyl)-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-glycine)]-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-valine)]-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-methylethyl)-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-phenylethyl)-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-t-butoxy)]-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-glycine)]-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-valine)]-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-phenylalanine)]-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-methylethyl)-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-phenylethyl)-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-t-butoxy)]-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-glycine)]-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-valine)]-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-phenylalanine)]-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-methyl-4-(2-carboxy-1-methylethyl)-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-methyl-4-(2-carboxy-1-phenylethyl)-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-glycine)]-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-valine)]-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-methylethyl)-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-phenylethyl)-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-glycine)]-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-valine)]-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-methylethyl)-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-phenylethyl)-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-glycine)]-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-valine)]-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-methylethyl)-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-phenylethyl)-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-glycine)]-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-valine)]-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-methylethyl)-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-phenylethyl)-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-t-butoxy)]-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-glycine)]-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-valine)]-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-phenylalanine)]-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-methylethyl)-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate

(±)-1,3-diphenyl-4-(2-carboxy-1-phenylethyl)-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-glycine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-valine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[3-keto-1-propyn-3-4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-methylethyl)-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-phenylethyl)-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-glycine)]-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-valine)]-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[3-keto-1-propyn-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-methylethyl)-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-phenylethyl)-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-glycine)]-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-valine)]-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(2-guanidinoethanethiol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate.

EXAMPLE 3 ##STR37##1-methyl-4-(2-carboxyethyl)-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate.

a) A magnetically stirred slurry of 45 mgs1-methyl-4-(2-carboxyethyl)-7-(N-boc-5-amino-1-pentynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionebenzyl ester (0.0924 mmol) in 2.0 mL ethyl acetate and 10 mgs of 10%palladium on carbon was stirred under an atmosphere of hydrogen for 3hours. The mixture was filtered, washing the solids with ethyl acetate,and concentrated in vacuo to yield 45 mgs (99%)1-methyl-4-(2-carboxyethyl)-7-(N-boc-5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionebenzyl ester. ¹ H NMR (CDCl₃, dTMS) 7.63 (1H, d, ⁴ J_(HH) =2 Hz, Ar--Ho-CON), 7.35-7.27 (6H, Ph, p-CON), 7.06 (1H, d, ³ J_(HH) =8 Hz, m-CON),5.11 (2H, s, OCH₂), 4.55 (1H, bs, BocNH), 3.98 (1H, d, ² J_(HH) =15 Hz,NCHHCO), 3.94 (2H, q, ³ J_(HH) =7 Hz, NCH₂), 3.80 (1H, d, ² J_(HH) =15Hz, NCHHCO), 3.35 (3H, s, NCH₃), 3.08 (2H, q, ³ J_(HH) =6.5 Hz,BocNHCH₂), 2.88-2.67 (2H, m, CH₂ CO₂), 2.62 (2H, t, ³ J_(HH) =8 Hz,ArCH₂), 1.65 (2H, p, ³ J_(HH) =8 Hz), 1.49 (2H, p, ³ J_(HH) =8 Hz), 1.42(9H, s, t-Bu), 1.35 (2H, p, ³ J_(HH) =8 Hz). ¹³ C NMR (CDCl₃, δTMS)171.2, 168.9, 167.3, 140.1, 138.8, 135.6, 132.2, 130.2, 128.5, 128.4,128.3, 120.9, 66.6, 52.3, 45.1, 40.4, 34.9, 34.8, 32.9, 30.7, 29.9,28.4, 26.4.

Using the above procedure, but substituting the appropriate7-alkynyl-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione for1-methyl-4-(2-carboxyethyl)-7-(N-boc-5-amino-1-pentynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionebenzyl ester there may be prepared, for example, the followingcompounds:

1-methyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-methyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-benzyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5dione,

1-benzyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyphanylalanyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-isopropyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-isopropyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-methyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-methyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-benzyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-benzyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-cyano-1-pentyl-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-isopropyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-isopropyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-methyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-methyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-benzyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-benzyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-isopropyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-isopropyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-methyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-methyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[N-[2-N-Boc)-aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-benzyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-benzyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[N-[2(N-Boc)-aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-isopropyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-isopropyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-methyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-methyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-benzyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-benzyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-isopropyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-isopropyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-methyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-methyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione

(±)-1-methyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione

(±)-1-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-benzyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-benzyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione

(±)-1-benzyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-isopropyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-isopropyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-methyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-methyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-benzyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-benzyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-isopropyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-isopropyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-methyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione

1-methyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione

(±)-1-methyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione

1-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione

(±)-1-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,-p01-benzyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-benzyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione

(±)-1-benzyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-isopropyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-isopropyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-methyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-methyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione

(±)-1-methyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione

(±)-1-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-benzyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-benzyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione

(±)-1-benzyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-isopropyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-isopropyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione

(±)-1,3-diphenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione

(±)-1-isopropyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-(N-Boc)-amino-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-cyano-1-pentyl-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-cyano-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-(3-cyanophenyl)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[N-[2-(N-Boc)aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[N-[2-(N-Boc)aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[N-[2-(N-Boc)aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[N-[2-(N-Boc)aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[N-[2-(N-Boc)aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[N-[2-(N-Boc)aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[N-[2-(N-Boc)aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[N-[2-(N-Boc)-aminoethane]-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione

(±)-1,3-diphenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[3-keto-1-propyl-3-[4-(N-Boc)-1-piperizine]]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione

(±)-1-isopropyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione

(±)-1-isopropyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-[2-(N-Boc)aminoethanethiol]-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione

(±)-1-benzyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[2-(4-cyanothiophenol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[4-[2-(N-Boc)amino-6-methylpyrimidine-4-yl]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-methyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-diphenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-diphenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1,3-diphenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-(3-ethoxy-1-methyl-3-oxo-1-propyl)-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-(3-ethoxy-1-phenyl-3-oxo-1-propyl)-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-t-butoxy-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyglycinyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyvalinyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-isopropyl-3-phenyl-4-[2-(1-benzyloxyphenylalanyl-4-benzyloxy)succinyl)]-7-[5-[2-(N-Boc)aminopyridine-3-yl]-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

b)1-methyl-4-(2-carboxyethyl)-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate was prepared using the method described in part (g) ofexample 1. Thus, 45 mgs1-methyl-4-(2-carboxyethyl)-7-(N-boc-5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionebenzyl ester yielded 36 mgs (93%)1-methyl-4-(2-carboxyethyl)-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate (1/2" C-18 reverse-phase column, eluting with a solventgradient of 10:90 acetonitrile(0.1% trifluroacetic acid)/water (0.1%trifluroacetic acid), time 0 to 10 min, to 50:50 acetonitrile(0.1%trifluroacetic acid)/water (0.1% trifluroacetic acid), time 10 min to 40min, flow=10 ml/min, R_(t) =30.3 min, υν detection 254 nm). HRMS (FAB)molecular ion m/z=348.1931 (cald. C₁₈ H₂₅ N₃ O₄, 348.1923) ¹ H NMR(CDCl.sub. 3, δTMS) 7.39 (1H, bs, Ar-H o-CON), 7.34 (1H, d, ³ J_(HH) =8Hz, p-CON), 7.16 (1H, d, ³ J_(HH) =8 Hz, m-CON), 4.00-3.90 (2H, m,NCHHCO, NCHHCH₂), 3.67 (1H, d, ² J_(HH) =16 Hz, NCHHCO), 3.56 (1H, dt, ²J_(HH) =14 Hz, ³ J_(HH) =6 Hz, NCHHCH₂) 3.17 (3H, s, NCH₃), 2.82 (2H, t,³ J_(HH) =7 Hz, H₃ NCH₂), 2.67-2.47 (4H, m CH₂ CO₂, ArCH₂), 1.57-1.42(4H, bs), 1.16 (2H, p, ³ J_(HH) =7 Hz).

Using the above procedure, but substituting the appropriate3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione for1-methyl-4-(2-carboxyethyl)-7-(N-boc-5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionebenzyl ester there could be prepared, for example, the followingcompounds:

1-methyl-4-(2-carboxy-1-methylethyl)-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-methyl-4-(2-carboxy-1-phenylethyl)-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-t-butoxy)]-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-glycine)]-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-valine)]-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-phenylalanine)]-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-methylethyl)-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-phenylethyl)-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-glycine)]-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-valine)]-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-methylethyl)-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-phenylethyl)-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-t-butoxy)]-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-glycine)]-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-valine)]-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-phenylalanine)]-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-methylethyl)-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-phenylethyl)-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-t-butoxy)]-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-glycine)]-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-valine)]-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-phenylalanine)]-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoracetate,

1-methyl-4-(2-carboxy-1-methylethyl)-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-methyl-4-(2-carboxy-1-phenylethyl)-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-t-butoxy)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-glycine)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-valine)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-phenylalanine)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-methylethyl)-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-phenylethyl)-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-glycine)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-valine)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-methylethyl)-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-phenylethyl)-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-t-butoxy)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-glycine)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-valine)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-phenylalanine)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-methylethyl)-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-phenylethyl)-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-t-butoxy)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-glycine)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-valine)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-phenylalanine)]-7-[N-(2-aminoethane)-3-keto-1-propyn-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-methyl-4-(2-carboxy-1-methylethyl)-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-methyl-4-(2-carboxy-1-phenylethyl)-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-t-butoxy)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-glycine)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-valine)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-phenylalanine)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-methylethyl)-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-phenylethyl)-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-glycine)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-valine)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-methylethyl)-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-phenylethyl)-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-t-butoxy)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-glycine)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-valine)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-phenylalanine)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-methylethyl)-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-phenylethyl)-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-t-butoxy)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-glycine)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-valine)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-phenylalanine)]-7-[3-keto-1-propyn-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-methyl-4-(2-carboxy-1-methylethyl)-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-methyl-4-(2-carboxy-1-phenylethyl)-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-glycine)]-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-valine)]-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-methylethyl)-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-phenylethyl)-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-glycine)]-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-valine)]-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-methylethyl)-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-phenylethyl)-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-glycine)]-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-valine)]-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-methylethyl)-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-phenylethyl)-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-glycine)]-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-valine)]-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-methyl-4-(2-carboxy-1-methylethyl)-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-methyl-4-(2-carboxy-1-phenylethyl)-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-t-butoxy)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-glycine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-valine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-phenylalanine]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-methylethyl)-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-phenylethyl)-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-glycine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-valine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-methylethyl)-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-phenylethyl)-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-t-butoxy)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-glycine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-valine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-phenylalanine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-methylethyl)-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-phenylethyl)-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-t-butoxy)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-glycine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-valine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-phenylalanine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-methyl-4-(2-carboxy-1-methylethyl)-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-methyl-4-(2-carboxy-1-phenylethyl)-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-t-butoxy)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-glycine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-valine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-phenylalanine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-methylethyl)-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-phenylethyl)-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-glycine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-valine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-methylethyl)-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-benzyl-4-(2-carboxy-1-phenylethyl)-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-t-butoxy)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-glycine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-valine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-phenylalanine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-methylethyl)-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-phenylethyl)-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-t-butoxy)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-glycine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-valine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pently]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-phenylalanine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-methylethyl)-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-phenylethyl)-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-t-butoxy)]-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-glycine)]-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-valine)]-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-phenylalanine)]-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[N-(2-aminoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[N-(2-aminoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[N-(2-aminoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[N-(2-aminoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[N-(2-aminoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[N-(2-aminoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-methylethyl)-7-[N-(2-aminoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-phenylethyl)-7-[N-(2-aminoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[N-(2-aminoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-glycine)]-7-[N-(2-aminoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-valine)]-7-[N-(2-aminoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[N-(2-aminoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[N-(2-aminoethane-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[N-(2-aminoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[N-(2-aminoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[N-(2-aminoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[N-(2-aminoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[N-(2-aminoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[N-(2-aminoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[N-(2-aminoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[N-(2-aminoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[N-(2-aminoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[N-(2-aminoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[N-(2-aminoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[3-keto-1-propyl-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[3-keto-1-propyl-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[3-keto-1-propyl-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[3-keto-1-propyl-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[3-keto-1-propyl-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[3-keto-1-propyl-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-methylethyl)-7-[3-keto-1-propyl-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-phenylethyl)-7-[3-keto-1-propyl-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[3-keto-1-propyl-3-(1-piperizine)]-3,4-diydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-glycine)]-7-[3-keto-1-propyl-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-valine)]-7-[3-keto-1-propyl-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[3-keto-1-propyl-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[3-keto-1-propyl-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[3-keto-1-propyl-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[3-keto-1-propyl-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[3-keto-1-propyl-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[3-keto-1-propyl-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[3-keto-1-propyl-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[3-keto-1-propyl-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[3-keto-1-propyl-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[3-keto-1-propyl-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[3-keto-1-propyl-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[3-keto-1-propyl-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[3-keto-1-propyl-3-(1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-methylethyl)-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-phenylethyl)-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-glycine)]-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-valine)]-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(2-aminoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-methylethyl)-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-phenylethyl)-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-glycine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-valine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)]-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[4-(2-amino-6-methylpyrimidine-4-yl)-4-oxa-1-butyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-methylethyl)-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-phenylethyl)-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-glycine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-valine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[5-(2-aminopyridine-3-yl)-5-oxa-1-pentyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

c)1-methyl-4-(2-carboxyethyl)-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionewas prepared by the method described in example 2.

Thus, 18 mgs1-methyl-4-(2-carboxyethyl)-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneyielded 17 mgs (87%)1-methyl-4-(2-carboxyethyl)-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate (1/2" C-18 reverse-phase column, eluting with a solventgradient of 10:90 methanol(0.1% trifluroacetic acid)/ water (0.1%trifluroacetic acid), time 0 to 10 min, to 50:50 methanol(0.1%trifluroacetic acid)/water (0.1% trifluroacetic acid), time 10 min to 40min, flow=10 ml/min, R_(t) =38.5 min, υν detection 254 nm). HRMS (FAB)molecular ion m/z=390.2132 (cald. C₁₉ H₂₇ N₅ O₄, 390.2182)

Using the above procedure, but substituting the appropriate amino acidfor1-methyl-4-(2-carboxyethyl)-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionethere may be prepared, for example, the following compounds:

1-methyl-4-(2-carboxy-1-methylethyl)-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-methyl-4-(2-carboxy-1-phenylethyl)-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-t-butoxy)]-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-glycine)]-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-valine)]-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-phenylalanine)]-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-methylethyl)-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-phenylethyl)-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-glycine)]-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-valine)]-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-methylethyl)-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-phenylethyl)-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-t-butoxy)]-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-glycine)]-7-(5-guanidino-1-penty)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-valine)]-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-phenylalanine)]-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-methylethyl)-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-phenylethyl)-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-t-butoxy)]-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-glycine)]-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-valine)]-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-phenylalanine)]-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-methyl-4-(2-carboxy-1-methylethyl)-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-methyl-4-(2-carboxy-1-phenylethyl)-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-t-butoxy)]-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-glycine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-valine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-phenylalanine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-methylethyl)-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-phenylethyl)-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-glycine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-valine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-methylethyl)-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-phenylethyl)-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-t-butoxy)]-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-glycine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-valine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-phenylalanine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-methylethyl)-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-phenylethyl)-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-t-butoxy)]-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-glycine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-valine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-phenylalanine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-methyl-4-(2-carboxy-1-methylethyl)-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-methyl-4-(2-carboxy-1-phenylethyl)-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-t-butoxy)]-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-glycine)]-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-valine)]-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-phenylalanine)]-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-methylethyl)-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-phenylethyl)-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-glycine)]-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-valine)]-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-methylethyl)-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-phenylethyl)-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-t-butoxy)]-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-glycine)]-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-valine)]-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-phenylalanine)]-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-methylethyl)-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-phenylethyl)-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-t-butoxy)]-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-glycine)]-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-valine)]-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-phenylalanine)]-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-methyl-4-(2-carboxy-1-methylethyl)-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-methyl-4-(2-carboxy-1-phenylethyl)-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-glycine)]-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-valine)]-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-methylethyl)-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-phenylethyl)-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-glycine)]-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-valine)]-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-methylethyl)-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-phenylethyl)-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-glycine)]-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-valine)]-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-methylethyl)-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-phenylethyl)-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-glycine)]-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-valine)]-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-methylethyl)-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-phenylethyl)-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-t-butoxy)]-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-glycine)]-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-valine)]-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-phenylalanine)]-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine2,5-dione trifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-glycine)-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[N-(2-guanidnioethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-methylethyl)-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-phenylethyl)-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-glycine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazephine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-valine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,4-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[N-(2-guanidinoethane)-3-keto-1-propyl-3-amine]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-methylethyl)-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-phenylethyl)-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-glycine)]-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-valine)]-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[3-keto-1-propyl-3-(4-amidino-1-piperizine)]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-methylethyl)-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-phenylethyl)-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-glycine)]-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoracetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-valine)]-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(2-guanidinoethanethiol)-1-ethyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate.

EXAMPLE 4 ##STR38##1-(3-nitrobenzyl)-4-(2-carboxyethyl)-7-(5-amino-1-pentynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate.

a) N-(2-amino-5-iodobenzoyl)-b-alanine ethyl ester was prepared usingthe method described in part (b) of example 1. Thus, from 21.0 grams of6-iodoisatoic anhydride (0.73 mol) and 11.3 grams of β-alanine ethylester hydrogenchloride (0.73 mol) was prepared 9.1 grams (35%)N-(2-amino-5-iodobenzoyl)-β-alanine ethyl ester (mp=83°-85° C., TLC,SiO₂, 1:1 EtOAc/hexane, R_(f) =0.46, υν positive). ¹ H NMR (CDCl₃, dTMS)7.57 (1H, d, ⁴ J_(HH) =2 Hz, Ar-H o-CON), 7.42 (1H, dd, ³ J_(HH) =9 Hz,⁴ J_(HH) =2 Hz, Ar-H p-CON), 6.63 (1H, bs, CONH), 6.44 (1H, d, ³ J_(HH)=9 Hz, Ar-H m-CON), 5.57 (2H, bs, NH₂), 4.10 (2H, q, ³ J_(HH) =7 Hz,OCH₂), 3.63 (2H, q, ³ J_(HH) =6 Hz, NCH₂), 2.63 (2H, t, ³ J_(HH) =6 Hz,CH₂ CO₂), 1.14 (3H, t, ³ J_(HH) =7 Hz, CH₃).

b) A magnetically stirred solution of 1.2 gramsN-(2-amino-5-iodobenzoyl)-b-alanine ethyl ester (3.35 mmol), 0.43 mL2,6-lutidine (3.7 mmol), 0.713 grams 3-nitrobenyl bromide (3.3 mmol),and 20 mL dimethylformamide, under an atmosphere of nitrogen, was heatedto 50° C. for 24 hours. The reaction mixture was allowed to cool to roomtemperature, poured over 100 mL 10% citric acid, and extracted 3×75 mLether. The combined organics were dried over magnesium sulfate, filteredand concentrated in vacuo. The resulting residue was purified by columnchromatography, using silica gel, eluting with a solvent gradient of 1:4ethyl acetate/hexane to 1:1 ethyl acetate/hexane isolating the yellowband (TLC, SiO₂, 1:1 ethyl acetate/hexane, R_(f) =0.66, υν positive)characterized as N-[2-(3-nitrobenzyl)-5-iodobenzoyl]-β-alanine ethylester (1.1 grams, 66%, mp=104°-105° C.).

c) To a magnetically stirred solution of 1.0 gramsN-[2-(3-nitrobenzyl)-5-iodobenzoyl]-b-alanine ethyl ester (2.0 mmol), 5mL methylene chloride, 0.56 mL triethylamine (4.0 mmol) at -30° C. underan atmosphere of nitrogen was slowly added, via an addition funnel, 0.26mL α-bromoacetylbromide (3.0 mmol) as a solution in 4 mL methylenechloride. After 2 hours, the mixture was diluted with 35 mL methylenechloride and washed 2×75 mL 10% citric acid, 2×75 mL sat. sodiumbicarbonate, dried over magnesium sulfate, filtered and concentrated invacuo. The resulting residue was dissolved in 5 mL dimethylformamide andadded, via an addition funnel, to a slurry of 72 mgs sodium hydride (3.0mmol) in 1.0 mL dimethylformamide cooled to 0° C. The reaction wasallowed to warm to room temperature. After 2 hours, the mixture waspoured over 100 mL of an ice cooled solution of 10% citric acid andextracted 3×75 mL ethyl acetate. The combined organics were washed with1×50 mL sat. sodium bicarbonate, dried over magnesium sulfate, andconcentrated in vacuo. The resulting residue was further purified bycolumn chromatography, using silica gel, eluting with a solvent gradientof 40:60 ethyl acetate/hexane to 70:30 ethyl acetate/hexane to yield0.45 grams (55%)1-(3-nitrobenzyl)-4-(2-carboxyethyl)-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester (TLC, SiO₂, 1:1 ethyl acetate/hexane, R_(f) =0.39, unpositive) and 0.18 grams of recoveredN-[2-(3-nitrobenzyl)-5-iodobenzoyl]-β-alanine ethyl ester. ¹ H NMR(CDCl₃, dTMS) 8.09 (1H, d, ⁴ J_(HH) =2 Hz, o-CON), 8.06 [1H, dt, ³J_(HH) =7 Hz, ⁴ J_(HH) =2 Hz, NCH₂ (C4-Ar-H)], 8.00 [1H, bs, NCH₂(C2-Ar-H)],7.73 (1H, dd, ³ J_(HH) =9 Hz, ⁴ J_(HH) =2 Hz, Ar-H p-CON),7.5-7.4 [2H, m, NCH₂ (C5, C6-Ar-H)], 6.88 (1H, d, ³ J_(HH) =9 Hz, Ar-Hm-CON), 5.20 (1H, d, ² J_(HH) =16 Hz, NCHHAr), 5.03 (1H, d, ² J_(HH) =16Hz, NCHHAr), 4.15 (1H, d, ² J_(HH) =15 Hz, NCHHCO), 4.10 (2H, q, ³J_(HH) =7 Hz, OCH₂), 3.96 (1H, d, ² J_(HH) =15 Hz, NCHHCO), 3.98-3.92(2H, m, NCH₂ CH₂), 2.71 (1H, dt, ² J_(HH) =16 Hz, ³ J_(HH) =8 Hz,CHHCO2), 2.63 (1H, dt, ² J_(HH) =16 Hz, ³ J_(HH) =8 Hz, CHHCO2), 1.22(3H, t, ³ J_(HH) =7 Hz, CH₃). ¹³ C NMR (CDCl₃, dTMS) 171.2, 168.3,165.3, 148.4, 141.0, 139.7, 139.0, 138.5, 132.8, 131.1, 129.9, 122.9,122.8, 121.9, 90.5, 60.8, 52.1, 50.3, 45.2, 32.7, 14.1.

d)1-(3-nitrobenzyl)-4-(2-carboxyethyl)-7-(N-boc-5-amino-1-pentynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester was prepared using the method described in part (f) ofexample 1. Thus, from 0.205 grams of1-(3-nitrobenzyl)-4-(2-carboxyethyl)-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester was prepared 168.2 mgs (57%)1-(3-nitrobenzyl)-4-(2-carboxyethyl)-7-(N-boc-5-amino-1-pentynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester (TLC, SiO₂, 1:1 ethyl acetate/hexane, R_(f) =0.36, υνpositive). ¹ H NMR (CDCl₃, dTMS, 8.09 [1H, dt, ³ J_(HH) =7 Hz, ⁴ J_(HH)=2 Hz, NCH₂ (C4-Ar-H)], 8.02 [1H, bs, NCH₂ (C2-Ar-H)], 7.81 (1H, d, ⁴J_(HH) =2 Hz, o-CON), 7.50-7.35 [3H, m, NCH₂ (C5,C6-Ar-H), Ar-H p-CON] ,7.04 (1H, d, ³ J_(HH) =9 Hz, Ar-H m-CON), 5.22 (1H, d, ² J_(HH) =16 Hz,NCHHAr), 5.04 (1H, d, ² J_(HH) =16 Hz, NCHHAr), 4.70 (1H, bs, BocNH),4.40 (1H, d, ² J_(HH) =12 Hz, NCHHCO), 4.12 (2H, q, ³ J_(HH) =7 Hz,OCH₂), 3.96 (1H, d, ² J_(HH) =12 Hz, NCHHCO), 4.0-3.8 (2H, m, NCH₂ CH₂),3.23 (2H, q, ³ J_(HH) =6 Hz, BocNHCH₂), 2.72 (1H, dt, ² J_(HH) =17 Hz, ³J_(HH) =8 Hz, CHHCO₂), 2.62 (1H, dt, ² J_(HH) =17 Hz, ³ J_(HH) =8 Hz,CHHCO2), 2.41 (2H, t, ³ J_(HH) =7 Hz, C∫CCH₂), 1.74 (2H, p, ³ J_(HH) =7Hz, CH₂ CH₂ CH₂), 1.40 (9H, s, t-Bu), 1.24 (3H, t, ³ J_(HH) =7 Hz, CH₃).¹³ C NMR (CDCl₃, δTMS) 171.2, 168.4, 166.2, 155.9, 148.4, 138.6, 138.2,134.9, 134.2, 132.8, 129.9, 129.5, 122.7, 122.4, 122.0, 121.2, 91.4,79.2, 60.8, 52.2, 50.4, 45.2, 39.8, 32.7, 28.7, 28.4, 16.8, 14.1.

e)1-(3-nitrobenzyl)-4-(2-carboxyethyl)-7-(5-amino-1-pentynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate was prepared using the method described in part (g) ofexample 1. Thus, 84 mgs1-(3-nitrobenzyl)-4-(2-carboxyethyl)-7-(N-boc-5-amino-1-pentynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester (0.142 mmol) yielded 75 mgs (91%)1-(3-nitrobenzyl)-4-(2-carboxyethyl)-7-(5-amino-1-pentynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate (1/2" C-18 reverse-phase column, eluting with a solventgradient of 10:90 methanol(0.1% trifluroacetic acid)/water (0.1%trifluroacetic acid), time 0 to 10 min, to 50:50 methanol(0.1%trifluroacetic acid)/water (0.1% trifluroacetic acid), time 10 min to 40min, flow=10 ml/min, R_(t) =45.1 min, υν detection 254 nm). HRMS (FAB)molecular ion m/z=465.1744 (cald. C₂₄ H₂₅ N₄ O₆, 465.1774) ¹ H NMR (CD₃CN, δTMS) 8.07 [1H, dt, ⁴ J_(HH) =2 Hz, ³ J_(HH) =7 Hz, NCH₂ (C4-Ar-H)],8.02 [1H, bs, NCH₂ (C2-Ar-H)]; 7.73 (1H, d, ⁴ J_(HH) =2 Hz,o-CON),7.60-7.50 [3H, m, NCH₂ (C5,C6-Ar-H), Ar-H p-CON], 7.25 (1H, d, ³ J_(HH)=9 Hz, Ar-H m-CON), 5.40 (1H, d, ² J_(HH) =15 Hz, NCHHAr), 5.00 (1H, d,² J_(HH) =15 Hz, NCHHAr), 4.13 (1H, d, ² J_(HH) = 12 Hz, NCHHCO),4.0-3.6 (3H, m, NCHHCO, NCH₂ CH₂), 3.1 (2H, bs, NH₃ CH₂), 2.65 (2H, t, ³J_(HH) =7 Hz, CH₂ CO₂), 2.41 (2H, t, ³ J_(HH) =7 Hz, C∫CCH₂), 1.9 (2H,p, ³ J_(HH) =7 Hz, CH₂ CH₂ CH₂).

EXAMPLE 5 ##STR39##1-(3-nitrobenzyl)-4-(2-carboxyethyl)-7-(5-guanidino-1-pentynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate

1-(3-nitrobenzyl)-4-(2-carboxyethyl)-7-(5-guanidino-1-pentynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate was prepared using the method described in example 2.Thus, 30 mgs of1-(3-nitrobenzyl)-4-(2-carboxyethyl)-7-(5-amino-1-pentynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate yielded 14 mgs (44%) of1-(3-nitrobenzyl)-4-(2-carboxyethyl)-7-(5-guanidino-1-pentynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate (1/2" C-18 reverse-phase column, eluting with a solventgradient of 20:80 methanol (0.1% trifluroacetic acid)/water (0.1%trifluroacetic acid), time 0 to 10 min, to 70:30 methanol (0.1%trifluroacetic acid)/water (0.1% trifluroacetic acid), time 10 min to 40min, flow=10 ml/min, R_(t) =33.8 min, υν detection 254 nm). HRMS (FAB)molecular ion m/z=507.2007 (cald. C₂₅ H₂₇ N₆ O₆, 507.1992) ¹ H NMR (CD₃CN/CD₃ OD, dTMS) 8.04 [1H, d, ³ J_(HH) =7 Hz, NCH₂ (C4-Ar-H)], 7.98 [1H,bs, NCH₂ (C2-Ar-H)], 7.68 (1H, d, ⁴ J_(HH) =2 Hz,o-CON), 7.60-7.40 [3H,m, NCH₂ (C5,C6-Ar-H), Ar-H p-CON], 7.25 (1H, d, ³ J_(HH) =9 Hz, Ar-Hm-CON), 5.37(1H, d, ² J_(HH) =15 Hz, NCHHAr), 5.00 (1H, d, ² J_(HH) =15Hz, NCHHAr), 4.13 (1H, d, ² J_(HH) =12 Hz, NCHHCO), 4.0-3.6 (3H, m,NCHHCO, NCH₂ CH₂), 3.24 (2H, bs, H₂ N(H₂ N═)NHCH₂), 2.65 (2H, t, CH₂CO₂), 2.41 (2H, t, C∫CCH₂), 1.9 (2H, p, ³ J_(HH) =7 Hz, CH₂ CH₂ CH₂).

EXAMPLE 6 ##STR40##1-(methyl)-4-(2-carboxyethyl)-7-(6-guanidino-1-hexynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate

a) N-(2-methylamino-5-iodobenzoyl)-β-alanine ethyl ester was preparedusing the method described in part (c) of example 1. Thus, 0.5 gramsN-(2-amino-5-iodobenzoyl)-β-alanine ethyl ester yielded 204.5 mgs (39%)of N-(2-methylamino-5-iodobenzoyl)-β-alanine ethyl ester (TLC, SiO₂, 1:1ethyl acetate/hexane R_(f) =0.67) and 253.2 mgs of a 7:1 mixture ofN-(2-amino-5-iodobenzoyl)-β-alanine ethyl ester andN-(2-dimethylamino-5-iodobenzoyl)-β-alanine ethyl ester (TLC, SiO₂, 1:1ethyl acetate/hexane R_(f) =0.46, υν positive). ¹ H NMR (CDCl₃, δTMS)7.6-7.5 (2H, m, Ar-H o,p-CON), 7.43 (1H, bs, NHMe), 6.62 (1H, bt, CONH),6.42 (1H, d, ³ J_(HH) =9 Hz, Ar-H m-CON), 4.18 (2H, q, ³ J_(HH) =7 Hz,OCH₂), 3.63 (2H, q, ³ J_(HH) =6 Hz, NCH₂ ), 2.81 (3H, d, ³ J_(HH) =5 Hz,NCH₃), 2.61 (2H, t, ³ H_(HH) =6 Hz, CH₂ CO₂), 1.28 (3H, t, ³ J_(HH) =7Hz, CH₃).

b)1-methyl-4-(2-carboxyethyl)-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester was prepared using the method described in part (d) ofexample 1. Thus, 1.9 grams of N-(2-methylamino-5-iodobenzoyl)-b-alanineethyl ester yielded 0.91 grams (43%) of1-methyl-4-(2-carboxyethyl)-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester (TLC, SiO₂, 1:1 ethyl acetate/hexane R_(f) =0.36, υνpositive). ¹ H NMR (CDCl₃, δTMS) 8.14 (1H, d, ⁴ J_(HH) =2 Hz, Ar-Ho-CON), 7.79 (1H, dd, ⁴ J_(HH) =2 Hz, ³ J_(HH) =9 Hz, Ar-H p-CON), 6.92(1H, d, ³ J_(HH) =9 Hz, Ar-H m-CON), 4.13 (2H, q, ³ J_(HH) =7 Hz, OCH₂),4.01 (1H, d, ² J_(HH) =15 Hz, COCHHN), 3.90 (2H, dt, ³ J_(HH) =8 Hz,J_(HH) =2 Hz, NCH₂), 3.87 (1H, d, ² J_(HH) =15 Hz, COCHHN), 3.34 (3H, s,NCH₃), 2.74 (1H, dt, ² J_(HH) =17 Hz, ³ J_(HH) =7 Hz, CHHCO₂), 2.63 (1H,dt, ² J_(HH) =17 Hz, ³ J_(HH) =7 Hz, CHHCO₂), 1.24 (3H, t, ³ J_(HH) =7Hz, CH₃).

c) To a magnetically stirred slurry of 2.94 grams lithium aluminumhydride (0.077 mol) in 150 mL ether cooled to 0° C. was slowly added,via an addition funnel, 6 grams of 5-cyano-1-pentyne (0.065 mol) in 15mL ether. The reaction mixture was allowed to warm to room temperature.After 1 hour, the reaction was cooled to 0° C. and quenched with 3.1 mLwater, 2.33 mL 20% sodium hydroxide, 10.83 mL water added in succession.After an additional 30 minutes, the slurry was filtered, washing thesalts with 40 mL ether. The ether was distilled at atmospheric pressureto leave an oil, which was further purified by Kugelrohr distillation(oven temp.ca. 145° C.) to yield 3.99 grams 6-amino-1-hexyne (64%).

d) To a magnetically stirred solution of 3.99 grams of 6-amino-1-hexyne(0.0413 mol) in 50 mL tetrahydrofuran was added 9.1 grams ofdi-tert-butyl dicarbonate (0.042 mol). After 2 hours, the reactionmixture was concentrated in vacuo and the resulting residuechromatographed, using silica gel, eluting with 1:1 ether/hexane toyield 3.4 grams (42%) N-boc-6-amino-1-hexyne (TLC, SiO₂, 1:1ether/hexane, R_(f) =0.5, ninhydrin char). ¹ H NMR (CDCl₃, δTMS) 4.55(1H, bs, BocNH), 3.13 (2H, bq, ³ J_(HH) =5 Hz, BocNHCH₂), 2.21 (2H, dt,⁴ J_(HH) =3 Hz, ³ J_(HH) =7 Hz, C∫CCH₂), 1.95 (1H, t, ⁴ J_(HH) =3 Hz,C∫CH), 1.6 (4H, m, CH₂ CH₂ CH₂ CH₂), 1.42 (9H, s, t-Bu).

e)1-(methyl)-4-(2-carboxyethyl)-7-(N-boc-6-amino-1-hexynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester was prepared using the method described in part (f) ofexample 1. Thus, 0.126 grams of1-methyl-4-(2-carboxyethyl)-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester and 0.119 grams of N-boc-6-amino-1-hexyne yielded 0.124grams (84%)1-(methyl)-4-(2-carboxyethyl)-7-(N-boc-6-amino-1-hexynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester (TLC, SiO₂, 1:1 ethyl acetate/hexane, R_(f) =0.36, υνpositive). ¹ H NMR (CDCl₃, δTMS) 7.84 (1H, d, ⁴ J_(HH) =2 Hz, Ar-Ho-CON), 7.47 (1H, dd, ⁴ J_(HH) =2 Hz, ³ J_(HH) =9 Hz, Ar-H p-CON), 7.07(1H, d, ³ J_(HH) =9 Hz, Ar-H m-CON), 4.60 (1H, bs, NH), 4.12 (2H, q, ³J_(HH) =7 Hz, OCH₂), 4.0 (1H, d, ² J_(HH) =15 Hz, NCHHCO), 3.90 (2H, t,³ J_(HH) =7 Hz, NCH₂), 3.84 (1H, d, ² J_(HH) =15 Hz, NCHHCO), 3.26 (3H,s, NCH₃), 3.15 (2H, q, ³ J_(HH) =7 Hz, BocNHCH₂), 2.73 (1H, dt, ² J_(HH)=16 Hz, ³ J_(HH) =9 Hz, CHHCO₂), 2.63 (1H, dt, ² J_(HH) =16 Hz, ³ J_(HH)=9 Hz, CHHCO₂), 2.40 (2H, t, ³ J_(HH) =6 Hz, C∫CCH₂), 1.62 (4H, m, CH₂CH₂ CH₂ CH₂), 1.24 (3H, t, ³ J_(HH) =7 Hz, CH₃).

f)1-(methyl)-4-(2-carboxyethyl)-7-(6-amino-1-hexynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate was prepared using the method described in part (g) ofexample 1. Thus, 62 mgs of1-(methyl)-4-(2-carboxyethyl)-7-(N-boc-6-amino-1-hexynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester yielded 50 mgs (83%)1-(methyl)-4-(2-carboxyethyl)-7-(6-amino-1-hexynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate (1/2" C-18 reverse-phase column, eluting with a solventgradient of 20:80 methanol (0.1% trifluroacetic acid)/water (0.1%trifluroacetic acid), time 0 to 10 min, to 70:30 methanol (0.1%trifluroacetic acid)/water (0.1% trifluroacetic acid), time 10 min to 40min, flow=10 ml/min, R_(t) =26.2 min, υν detection 254 nm). HRMS (FAB)molecular ion m/z=358.1761 (cald. C₁₉ H₂₄ N₃ O₄, 358.1767). ¹ H NMR (D₂O,) 7.47 (1H, d, ⁴ J_(HH) =2 Hz, Ar-H o-CON), 7.37 (1H, dd, ⁴ J_(HH) =2Hz, ³ J_(HH) =9 Hz, Ar-H p-CON), 7.12 (1H, d, ³ J_(HH) =9 Hz, Ar-Hm-CON), 3.95-3.8 (2H, m, NCHHCO, NCHHCH₂), 3.63 (1H, d, ² J_(HH) =15 Hz,NCHHCO), 3.52 (1H, dt, ² J_(HH) =15 Hz, ³ J_(HH) =5 Hz, NCHHCO₂), 3.16(3H, s, NCH₃), 2.85 (2H, t, ³ J_(HH) =7 Hz, NH₃ CH₂), 2.6-2.4 (2H, m,CH₂ CO₂), 2.28 (2H, t, ³ J_(HH) =6 Hz, C∫CCH₂), 1.62 & 1.47 (each 2H, p,³ J_(HH) =6 Hz, CH₂ CH₂ CH₂ CH₂).

g)1-(methyl)-4-(2-carboxyethyl)-7-(6-guanidino-1-hexynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate was prepared by the method described in example 2. Thus,from 25 mgs1-(methyl)-4-(2-carboxyethyl)-7-(6-amino-1-hexynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate was prepared 22 mgs (71%) of1-(methyl)-4-(2-carboxyethyl)-7-(6-guanidino-1-hexynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate (1/2" C-18 reverse-phase column, eluting with a solventgradient of 20:80 methanol (0.1% trifluroacetic acid)/water (0.1%trifluroacetic acid), time 0 to 10 min, to 70:30 methanol (0.1%trifluroacetic acid)/water (0.1% trifluroacetic acid), time 10 min to 40min, flow=10 ml/min, R_(t) =28.6 min, un detection 254 nm). HRMS (FAB)molecular ion m/z=400.1956 (cald. C₂₀ H₂₆ N₅ O₄, 400.1985). ¹ H NMR (D₂O,) 7.58 (1H, d, ⁴ J_(HH) =2 Hz, Ar-H o-CON), 7.43 (1H, dd, ⁴ J_(HH) =2Hz, ³ J_(HH) =9 Hz, Ar-H p-CON), 7.20 (1H, d, ³ J_(HH) =9 Hz, Ar-Hm-CON), 4.05-3.95 (2H, m, NCHHCO₂, NCHHCH₂), 3.71 (1H, d, ² J_(HH) =15Hz, NCHHCO), 3.56 (1H, dt, ² J_(HH) =15 Hz, ³ J_(HH) =5 Hz, NCHHCO₂),3.19 (3H, s, NCH₃), 3.06 (2H, t, ³ J_(HH) =7 Hz, H₂ N(H₂ N═)CNHCH₂),2.7-2.5 (2H, m, CH₂ CO₂), 2.32 (2H, t, ³ J_(HH) =6 Hz, C∫CCH₂), 1.60 &1.49 (each 2H, p, ³ J_(HH) =6 Hz, CH₂ CH₂ CH₂ CH₂).

EXAMPLE 7 ##STR41##1-(3-nitrobenzyl)-4-(2-carboxyethyl)-7-(6-amino-1-hexynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifuroacetate.

a)1-(3-nitrobenzyl)-4-(2-carboxyethyl)-7-(N-boc-6-amino-1-hexynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester was prepared using the method described in part (f) ofexample 1. Thus, from 0.26 grams of1-(3-nitrobenzyl)-4-(2-carboxyethyl)-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester and 0.19 grams of N-boc-6-amino-1-hexyne was prepared 226.3mgs (78%)1-(3-nitrobenzyl)-4-(2-carboxyethyl)-7-(N-boc-6-amino-1-hexynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester (TLC, SiO₂, 1:1 ethyl acetate/hexane, R_(f) =0.34, υνpositive). ¹ H NMR (CDCl₃, δTMS) 8.09 [1H, dt, ³ J_(HH) =7 Hz, ⁴ J_(HH)=2 Hz, NCH₂ (C4-Ar-H)], 8.02 [1H, bs, NCH₂ (C2-Ar-H)], 7.83 (1H, d, ⁴J_(HH) =2 Hz, o-CON), 7.50-7.35 [ 3H, m, NCH₂ (C5, C6-Ar-H), Ar-Hp-CON], 7.05 (1H, d, ³ J_(HH) =8 Hz, Ar-H m-CON), 5.22 (1H, d, ² J_(HH)=16 Hz, NCHHAr), 5.02 (1H, d, ² J_(HH) =16 Hz, NCHHAr), 4.60 (1H, bs,BocNH), 4.20-4.08 (3H, m, NCHHCO, OCH₂), 4.0-3.8 (3H, m, NCH₂ CH₂,NCHHCO), 3.16 (2H, q, ³ J_(HH) =6 Hz, BocNHCH₂), 2.72 (1H, dt, ² J_(HH)=16 Hz, ³ J_(HH) =8 Hz, CHHCO₂), 2.62 (1H, dt, ² J_(HH) =16 Hz, ³ J_(HH)=8 Hz, CHHCO2), 2.39 (2H, t, ³ J_(HH) =6 Hz, C∫CCH₂), 1.60 (4H, bs, CH₂CH₂ CH₂ CH.sub. 2), 1.41 (9H, s, t-Bu), 1.24 (3H, t, ³ J_(HH) =7 Hz,CH₃).

b)1-(3-nitrobenzyl)-4-(2-carboxyethyl)-7-(6-amino-1-hexynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate was prepared using the method described in part (g) ofexample 1. Thus, from 0.11 grams of1-(3-nitrobenzyl)-4-(2-carboxyethyl)-7-(N-boc-6-amino-1-hexynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester was prepared 90 mgs (79%) of1-(3-nitrobenzyl)-4-(2-carboxyethyl)-7-(6-amino-1-hexynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate (1/2" C-18 reverse-phase column, eluting with a solventgradient of 20:80 methanol(0.1% trifluroacetic acid)/water (0.1%trifluroacetic acid), time 0 to 10 min, to 70:30 methanol(0.1%trifluroacetic acid)/water (0.1% trifluroacetic acid), time 10 min to 40min, flow=10 ml/min, R_(t) =39.2 min, un detection 254 nm). HRMS (FAB)molecular ion m/z=479.1911 (cald. C₂₅ H₂₇ N₄ O.sub. 6, 479.1931). ¹ HNMR (D₂ O) 7.7 [1H, bd, ³ J_(HH) =8 Hz, NCH₂ (C4-Ar-H)], 7.58 [1H, bs,NCH₂ (C2-Ar-H)], 7.41 (1H, d, ⁴ J_(HH) =2 Hz, o-CON), 7.25-7.05 [3H, m,NCH₂ (C5,C6-Ar-H), Ar-H p-CON], 7.01 (1H, d, ³ J_(HH) =9 Hz, Ar-Hm-CON), 5.09 (1H, d, ² J_(HH) =16 Hz, NCHHAr), 4.8 (1H, d, NCHHAr,overlapping with HOD), 4.00 (1H, d, ² J_(HH) =14 Hz, NCHHCO), 3.9-3.65(2H, m, NCHHCO, NCHHCH₂), 3.6-3.5 (1H, m, NCHHCH₂), 2.83 (2H, t, ³J_(HH) =7 Hz, NH₃ CH₂), 2.51 (2H, t, ³ J_(HH) =7 Hz, CH₂ CO₂), 2.17 (2H,t, ³ J_(HH) =7 Hz, C∫CCH₂), 1.57 & 1.40 (each 2H, p, ³ J_(HH) =7 Hz, CH₂CH₂ CH₂ CH₂).

EXAMPLE 8 ##STR42##1-(3-nitrobenzyl)-4-(2-carboxyethyl)-7-(6-guanidino-1-hexynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate.

1-(3-nitrobenzyl)-4-(2-carboxyethyl)-7-(6-guanidino-1-hexynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate was prepared using the method described in example 2.Thus, 45 mgs of1-(3-nitrobenzyl)-4-(2-carboxyethyl)-7-(6-amino-1-hexynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate yielded 25 mgs (52%) of1-(3-nitrobenzyl)-4-(2-carboxyethyl)-7-(6-guanidino-1-hexynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate (1/2" C-18 reverse-phase column, eluting with a solventgradient of 20:80 methanol(0.1% trifluroacetic acid)/water (0.1%trifluroacetic acid), time 0 to 10 min, to 70:30 methanol(0.1%trifluroacetic acid)/water (0.1% trifluroacetic acid), time 10 min to 40min, flow=10 ml/min, R_(t) =41.3 min, υν detection 254 nm). HRMS (FAB)molecular ion m/z=521.2161 (cald. C₂₆ H₂₈ N₆ O₆, 521.2148). ¹ H NMR (D₂O) 7.86 [1H, dt, ⁴ J_(HH) =3 Hz, ³ J_(HH) =6 Hz, NCH₂ (C4-Ar-H)], 7.64[1H, bs, NCH₂ (C2-Ar-H)], 7.46 (1H, d, ⁴ J_(HH) =2 Hz, o-CON), 7.30-7.23[3H, m, NCH₂ (C5,C6-Ar-H), Ar-H p-CON], 7.18 (1H, d, ³ J_(HH) =8 Hz,Ar-H m-CON), 5.30 (1H, d, ² J_(HH) =16 Hz, NCHHAr), 4.7 (1H, NCHHAr,overlapping with HOD), 4.03 (1H, d, ² J_(HH) =14 Hz, NCHHCO), 3.85 (1H,dt, ² J_(HH) =14 Hz, ³ J_(HH) =7 Hz, NCHHCH₂), 3.74 (1H, d, ² J_(HH) =14Hz, NCHHCO), 3.55 (1H, dt, ² J_(HH) =14 Hz, ³ J_(HH) =7 Hz, NCHHCH₂),2.97 (2H, t, ³ J_(HH) =7 Hz, H₂ N(H₂ N═)NHCH₂), 2.49 (2H, t, ³ J_(HH) =7Hz, CH₂ CO₂), 2.21 (2H, t, ³ J_(HH) =7 Hz, C∫CCH₂), 1.48 & 1.38 (each2H, p, ³ J_(HH) =7 Hz, CH₂ CH₂ CH₂ CH₂).

EXAMPLE 9 ##STR43##1-(methyl)-4-(2-carboxyethyl)-7-[4-(aminomethyl)phenyl]ethynyl-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate.

a)1-(methyl)-4-(2-carboxyethyl)-7-(4-cyanophenyl)ethynyl-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester was prepared using the method employed in part (f) ofexample 1. Thus, from 0.41 grams of1-methyl-2-(carboxyethyl)-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester and 0.127 grams of (4-cyanophenyl)ethyne (Gilbert, J. C.;Weerasooriya, U. J. Org. Chem. 1979, 44, 4997-98) was prepared 0.205grams of1-(methyl)-4-(2-carboxyethyl)-7-(4-cyanophenyl)ethynyl-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester (mp=160°-161° C., TLC, SiO2, 1:1 ethyl acetate/hexane,Rf=0.30, υν positive). ¹ H NMR (CDCl₃, δTMS) 7.98 (1H, d, ⁴ J_(HH) =2Hz, Ar-Ho-CON), 7.65-7.50 (5H, m, Ar-H p-CON, Ar-H o,p-CN), 7.17 (1H, d,³ J_(HH) =9 Hz, m-CON), 4.09 (2H, q, ³ J_(HH) =7 Hz, OCH₂), 4.02 (1H, d,² J_(HH) =15 Hz, NCHHCO), 3.89 (2H, t, ³ J_(HH) =7 Hz, NCH₂ CH₂), 3.86(1H, d, ² J_(HH) =15 Hz, NCHHCO), 3.34 (3H, s, NCH₃), 2.72 (1H, dt, ²J_(HH) =16 Hz, ³ J_(HH) =7 Hz, CHHCO₂), 2.62 (1H, dt, ² J_(HH) =16 Hz, ³J_(HH) =7 Hz, CHHCO₂), 1.20 (3H, t, 3J_(HH) =7 Hz, CH₃). ¹³ C NMR(CDCl₃, δTMS) 171.2, 168.6, 166.2, 141.0, 134.8, 134.4, 132.0, 128.8,127.5, 121.1, 119.7, 118.3, 111.8, 91.7, 88.9, 60.3, 52.1, 45.1, 32.7,31.5, 14.1.

b) A magnetically stirred solution of 3 mL toluene, 6.8 mgs dicobaltoctacarbonyl (0.02 mmol) cooled to -20° C. was saturated withtriethylsilane via a gas bubbler. 0.1 grams of1-(methyl)-4-(2-carboxyethyl)-7-(4-cyanophenyl)ethynyl-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester (0.24 mmol) was added as a solution in 0.5 mL toluene andthe reaction mixture heated to 60° C. for 20 hours (Murai, T. et al.,Tetrahedron Lett. 1985, 26, 5145-48). The mixture was allowed to cool toroom temperature and concentrated in vacuo. The resulting residue wasdiluted with methanol and 2 mL of 2N sodium hydroxide was added. After30 minutes, the mixture was neutralized with 2 mL acetic acid,concentrated in vacuo, diluted with 2 mL of a 1:1 methanol/watersolution and purified by high-pressure liquid chromatography (1/2" C-18reverse-phase column, eluting with a solvent gradient of 20:80 methanol(0.1 % trifluroacetic acid)/water (0.1% trifluroacetic acid), time 0 to10 min, to 70:30 methanol (0.1% trifluroacetic acid)/water (0.1%trifluroacetic acid), time 10 min to 40 min, flow=10 ml/min, R_(t) =36.8min, un detection 254 nm) to yield 30.0 mgs (25%) of1-(methyl)-4-(2-carboxyethyl)-7-[4-(aminomethyl)phenyl]ethynyl-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate. ¹ H NMR (CD₃ OD) 7.68 (1H, d, ⁴ J_(HH) =2 Hz,Ar-Ho-CON), 7.48 (1H, dd, ⁴ J_(HH) =2 Hz, ³ J_(HH) =9 Hz, Ar-H p-CON)7.4-7.3 (4H, m, Ar-H o,p-CN), 7.17 (1H, d, m-CON), 4.02 (2H, s, ArCH₂N), 4.0-3.7 (4H, m, NCH₂ CO, NCH₂ CH₂), 3.0 (3H, s, NCH₃) 2.6 (2H, m,CH₂ CO₂).

Using the above procedure, but substituting the appropriate3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione nitrile for1-(methyl)-4-(2-carboxyethyl)-7-(4-cyanophenyl)ethynyl-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester there may be prepared, for example, the following compounds:

1-methyl-4-(2-carboxy-1-methylethyl)-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-methyl-4-(2-carboxy-1-phenylethyl)-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-glycine)]-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-valine)]-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-methylethyl)-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-phenylethyl)-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-glycine)]-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-valine)]-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-methylethyl)-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-phenylethyl)-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-glycine)]-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-valine)]-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-methylethyl)-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-phenylethyl)-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-glycine)]-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-valine)]-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-methyl-4-(2-carboxy-1-methylethyl)-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-methyl-4-(2-carboxy-1-phenylethyl)-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-glycine)]-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-valine)]-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-methylethyl)-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-phenylethyl)-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-glycine)]-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-valine)]-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-methylethyl)-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-phenylethyl)-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-glycine)]-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-valine)]-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-methylethyl)-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-phenylethyl)-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-glycine)]-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-valine)]-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-methylethyl)-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-phenylethyl)-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-glycine)]-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-valine)]-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(3-aminomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[2-(4-aminomethylthiophenol)-1-ethyne[-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-methylethyl)-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-phenylethyl)-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-glycine)]-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-valine)]-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(4-aminomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate.

EXAMPLE 10 ##STR44##1-(methyl)-4-(2-carboxyethyl)-7-[4-(guanidinomethyl)phenyl]ethynyl-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate

1-(methyl)-4-(2-carboxyethyl)-7-[4-(guanidinomethyl)phenyl]ethynyl-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate was prepared using the method described in example 2.Thus, from 15 mgs of1-(methyl)-4-(2-carboxyethyl)-7-[4-(aminomethyl)phenyl]ethynyl-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate was prepared 7 mgs (37%) of1-(methyl)-4-(2-carboxyethyl)-7-[4-(guanidinomethyl)phenyl]ethynyl-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate (1/2" C-18 reverse-phase column, eluting with a solventgradient of 20:80 methanol(0.1% trifluroacetic acid)/water (0.1%trifluroacetic acid), time 0 to 10 min, to 70:30 methanol(0.1%trifluroacetic acid)/water (0.1% trifluroacetic acid), time 10 min to 40min, flow=10 ml/min, R_(t) =39.6 min, un detection 254 nm). ¹ H NMR (CD₃OD, D₂ O) 7.50 (1H, d, ⁴ J_(HH) =2Hz, Ar--Ho-CON), 7.38 (1H, bd, ³J_(HH) =9 Hz, Ar--H p-CON) 7.20 (1H, d, ³ H_(HH) =9 Hz, m-CON), 7.15-7.0(4H, m, Ar--H o,p-CN), 4.23 (2H, s, ArCH₂ NHC(=NH₂)NH₂), 3.9-3.8 (2H, m,NCHHCO, NCHHCH₂), 3.72 (1H, d, 2JHH=16 Hz, NCHHCO), 3.58 (1H, m,NCHHCH₂), 3.12 (3H, s, NCH₃) 2.53 (2H, m, CH₂ CO₂).

Using the above procedure, but substituting the appropriate amino acidfor1-(methyl)-4-(2-carboxyethyl)-7-[4-aminomethyl)phenyl]ethynyl-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione trifluroacetate there may be prepared, forexample, the following compounds:

1-methyl-4-(2-carboxy-1-methylethyl)-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione,

1-methyl-4-(2-carboxy-1-phenylethyl)-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-glycine)]-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-valine)]-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-methylethyl)-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-phenylethyl)-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-glycine)]-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-valine)]-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-methylethyl)-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-phenylethyl)-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-glycine)]-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-valine)]-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-methylethyl)-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-phenylethyl)-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-glycine)]-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-valine)]-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-methyl-4-(2-carboxy-1-methylethyl)-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-methyl-4-(2-carboxy-1-phenylethyl)-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-glycine)]-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-valine)]-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-methylethyl)-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-phenyl-4-(2-carboxy-1-phenylethyl)-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-glycine)]-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-valine)]-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-methylethyl)-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-benzyl-4-(2-carboxy-1-phenylethyl)-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-glycine)]-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-valine)]-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-methylethyl)-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

1-isopropyl-4-(2-carboxy-1-phenylethyl)-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-glycine)]-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione trifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-valine)]-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-methylethyl)-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-phenylethyl)-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-glycine)]-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-valine)]-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,4-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(3-guanidinomethylphenyl)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-methyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-methylethyl)-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-(2-carboxy-1-phenylethyl)-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-glycine)]-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-valine)]-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1,3-diphenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-benzyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-methylethyl)-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-(2-carboxy-1-phenylethyl)-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-t-butoxy)]-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-glycine)]-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-valine)]-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate,

(±)-1-isopropyl-3-phenyl-4-[succin-2-yl-(1-phenylalanine)]-7-[2-(4-guanidinomethylthiophenol)-1-ethyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate.

EXAMPLE 11 ##STR45##1-methyl-4-(2-carboxy-1-methylethyl)-7-(5-guanidino-1-pentynyl)-3,4-dihydro-1H-1,4,benzodiazepine-2,5-dione trifluroacetate.

a) Methyl N-(2-amino-5-iodobenzoyl)-3-amino-3-methylpropanate wasprepared using the method described in part (b) of example 1. Thus, 1.72grams of 5-iodoisatoic anhydride and 1.73 grams of methyl3-aminobutanoate p-tosylate yielded 0.65 grams (30%) methylN-(2-amino-5-iodobenzoyl)-3-aminobutanoate (TLC, SiO₂, 1:1 EtOAc/hexane,R_(f) =0.63, υν positive).

b) Methyl N-(2-methylamino-5-iodobenzoyl)-3-amino-3-methylpropanoate wasprepared using the method described in part (c) of example 1. Thus, 0.32grams of methyl N-(2-amino-5-iodobenzoyl)-3-aminobutanoate yielded 0.14grams (43%) of methyl N-(2-methylamino-5-iodobenzoyl)-3-aminobutanoate(TLC, SiO₂, 1:1 EtOAc/hexane, R_(f) =0.85, υν positive).

c)1-methyl-4-(3-methoxy-3-oxobutan-2-yl)-7-iodo-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dionewas prepared using the method described in part (d) of example 1. Thus,0.25 grams of N-(2-methylamino-5-iodobenzoyl)-3-aminobutanoate yielded0.08 grams (29%) of1-methyl-4-(3-methoxy-3-oxobutan-2-yl)-7-iodo-3,4-dihydro-1H-1,4-benzo-diazapine-2,5-dione(TLC, SiO₂, 1:1 EtOAc/hexane, R_(f) =0.33, υν positive).

d)1-methyl-4-(3-methoxy-3-oxobutan-2-yl)-7-[5-(N-Boc)-amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionewas prepared using the method described in part (f) of example 1. Thus,0.08 grams of1-methyl-4-(3-methoxy-3-oxobutan-2-yl)-7-iodo-3,4-dihydro-1H-1,4-benzo-diazapine-2,5-dioneyielded 0.061 grams (68%) of1-methyl-4-(3-methoxy-3-oxobutan-2-yl)-7-[5-(N-Boc)-amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione(TLC, SiO₂, 1:1 EtOAc/hexane, R_(f) =0.24, un positive).

e)1-methyl-4-(2-carboxy-1-methylethyl)-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate was prepared using the method described in part (g) ofexample 1. Thus, 61 mgs of1-methyl-4-(3-methoxy-3-oxobutan-2-yl)-7-[5-(N-Boc)-amino-1-pentyne]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneyielded 40 mgs (87%) of1-methyl-4-(2-carboxy-1-methylethyl)-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate (1/2" C-18 reverse-phase column, eluting with a solventgradient of 10:90 methanol(0.1% trifluroacetic acid)/water(0.1%trifluroacetic acid), time 0 to 10 min, to 50:50 methanol(0.1%trifluroacetic acid)/water(0.1% trifluroacetic acid), time 10 min to 40min, flow 10 ml/min, R_(t) =31.2 min, υν detection 254 nM). HRMS (FAB)molecular ion m/z=358.1765 (cald. C₁₉ H₂₄ N₃ O₄ , 358.1767)

f)1-methyl-4-(2-carboxy-1-methylethyl)-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate was prepared using the method described in example 2.Thus, 15 mgs of1-methyl-4-(2-carboxy-1-methylethyl)-7-(5-amino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate yielded 10 mgs (67%) of1-methyl-4-(2-carboxy-1-methyllethyl)-7-(5-guanidino-1-pentyne)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluroacetate (1/2" C-18 reverse-column, eluting with a solventgradient of 10:90 methanol(0.1% trifluroacetic acid)/water(0.1%trifluroacetic acid), time 0 to 10 min, to 50:50 methanol(0.1%trifluroacetic acid)/water(0.1% trifluroacetic acid), time 10 min to 40min, flow 10 ml/min, R_(t) =36.9 min, υν detection 254 nM). HRMS (FAB)molecular ion m/z=400.1999 (cald. C₂₀ H₂₆ N₅ O₄, 400.1986).

EXAMPLE 12 ##STR46##1-(4-chlorophenyl)methyl-4-(2-carboxyethyl)-7-(4-(1-piperidin)-phenyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dionetrifluroacetate.

a) Over a period of 15 minutes samples of iodine (8.62 grams, 0.034 mol)and silver benzoate (7.78 grams, 0.034 mol) were added in portions to amagnetically stirred solution of 5 grams of 1-phenylpiperazine in 80 mLacetic acid. The mixture stirred for 1 hour. The solvent was evaporatedand the residue partioned between 150 mL diethyl ether and 150 mL 2Nsodium hydroxide. The organic layer was washed with 100 mL water, 100 mLbrine, then dried over potassium carbonate and concentrated in vacuo toyield 1.0 gram (11%) of 1-(4-iodophenyl)-piperzine (110°-115° C.). Thematerial obtained was used without further purification. ¹ H NMR (CDCl₃,dTMS) 7.51 (2H, d, ³ J_(HH) =9 Hz, m-ArH), 6.69 (2H, d, ³ J_(HH) =9 Hz,o-ArH), 3.17 (4H, m), 3.04 (4H, m). .sup. 13 C NMR (CDCl₃) 151.36,137.73, 118.05, 81.35, 49.92, 45.95.

b) The crude material obtained from part (a) (1 gram, 3.47 mmol) wasdissolved in dry THF (10 mL) and a catalytic amount ofdimethylaminopyridine (100 mgs) and di-tert-butyl dicarbonate (0.9grams, 4.1 mmol, 1.2 molar excess) were added, monitoring the reactionby TLC (SiO₂, 1:1 EtOAc/hexane, R_(f) (product)=0.88). After 12 hours(overnight) the reaction was diluted with diethyl ether and extracted1×75 mL water, 1×75 mL 1N HCl, 1×75 mL sat. sodium bicarbonate, 1×75 mLbrine, dried over potassium carbonate, filtered and concentrated invacuo. The material was further purified by filtering through a packetof SiO₂ using 1:1 diethyl ether/hexane as the eluting solvent to yield1-(4-iodophenyl)-4-(N-Boc)-piperzine (1 grm, 77%, 142°-143° C.). ¹ H NMR(CDCl₃, dTMS) 7.54 (2H, d, ³ J_(HH) =8 Hz, m-ArH), 6.69 (2H, d, ³ J_(HH)=8 Hz, o-ArH), 3.58 (4H, t, ³ J_(HH) =5 Hz), 3.04 (4H, t, ³ J_(HH) =5Hz) 1.48 (9H, s, Bu^(t)).

c) A magnetically stirred solution ofN-(2-amino-5-iodobenzoyl)-3-aminoproprionate (8.8 grams, 23.4 mmol),prepared using the procedure shown in part (b) of example 1,dimethylformamide, 2,6-lutidine (1.5 molar equiv., 35.1 mmol, 4.25 mL)and 4-chlorobenzyl chloride (1.5 molar equiv., 35.1 mmol, 5.96 grams)was heated to 100° C. for 24 hours. The mixture was allowed to cool toroom temperature and concentrated in vacuo. The resulting residue wasdissolved in 150 mL methylene chloride and washed with 2×100 mL 10%citric acid, 1×100 mL water, dried over sodium sulfate, filtered andconcentrated in vacuo. The solid obtained was dissolved in a minimumvolumn of methylene chloride and a 5 fold excess of hexanes added. Thesolution was allowed to stand overnight in the refrigerator (5°-7° C.)to yield 7.56 grams ofN-(2-(p-chlorobenzyl)amino-5-iodobenzoyl)-3-aminoproprionate (153°-155°C.). Concentration of the mother liquor and repeating the steps forcrystallization yielded a second crop (3.32 grams) for a total 92%isolated yield of the desired product. ¹ H NMR (CDCl₃, dTMS) 8.10 (1H,bt, ³ J_(HH) =5 Hz, NH), 7.60 (1H, d, ⁴ J_(HH) =2 Hz, C6-H), 7.44 (1H,dd, ³ J_(HH) =9 Hz, ⁴ J_(HH) =2 Hz, C8-H), 7.29 (4H, m, p-ClC6H4), 6.72(1H, bt, ³ J_(HH) =6 Hz, NH), 6.34 (1H, d, ³ J_(HH) =9 Hz, C9-H), 4.35(2H, d, ³ J_(HH) =9 Hz, NCH₂ Ar), 4.20 (2H, q, ³ J_(HH) =7 Hz, OCH₂),3.68 (2H, q, J_(HH) =6 Hz, NCH₂), 2.65 (2H, t, ³ J_(HH) =6, CH₂ CO₂),1.31 (3H, t, ³ J_(HH) =7 Hz, CH₂ CH₃). ¹³ C NMR (CDCl₃) 172.6, 168.3,148.6, 141.0, 137.0, 135.6, 128.8, 128.3, 117.6, 114.3, 75.1, 60.9,46.3, 35.1, 33.9, 14.2.

d) To a magnetically stirred biphasic solution ofN-(2-(p-chlorobenzyl)amino-5-iodobenzoyl)-3-aminoproprionate (10 grams,20.57 mmol), 200 mL methylene chloride, and 200 mL water was added, atroom temperature, α-bromoacetyl bromide (24.7 mmol, 1.2 molar equiv.,2.15 mL), monitoring the reaction by TLC (SiO₂, 1:1 EtOAc/hexane). Thereaction was complete 6 hours. The layers were separated, washing theaqueous layer with 75 mL methylene chloride. The combined organics werewashed 1×100 mL sat. sodium bicarbonate, 1×100 mL Brine, dried oversodium sulfate, filtered and concentrated in vacuo. The resultingresidue was dissolved in 50 mL dimethylformamide and added, via anaddition funnel, over a period of 30 minutes to a slurry of sodiumhydride (1.2 molar equiv., 24.7 mmol, 0.60 grams) in 10 mLdimethylformamide cooled to 0° C. under an atmosphere of nitrogen. Thereaction was stirred for an additional 1 hour and then poured over anice-cold 10% citric acid solution. The cloudy mixture was extracted3×100 mL EtOAc. The combined organics were dried over magnesium sulfate,filtered, and concentrated in vacuo. Purification was achieved by columnchromatography (SiO₂, 600 mL, using 30% EtOAc/70% hexane to 60%EtOAc/40% hexane as the eluting solvent gradient) to yield 6.5 grams(63%) of1-(p-chlorobenzyl)-7-iodo-4-(2-carboxyethyl)-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dioneethyl ester. ¹ H NMR (CDCl₃, dTMS) 8.11 (1 H, d, ³ J_(HH) =2 Hz, C6-H),6.68 (1H, dd, ⁴ J_(HH) =2 Hz, ³ J_(HH) =9 Hz, C8-H), 7.23 (2H, d, ³J_(HH) =8 Hz, ArH), 7.03 (2H, d, ³ J_(HH) =8 Hz, ArH), 6.87 (1H, d, ³J_(HH) =9 Hz, C9-H), 5.05 (1H, d, ² J_(HH) =16 Hz, NCHHAr), 4.95 (1H, d,2JHH=16 Hz, NCHHAr), 4.1 (3H, m, OCH2, C3-H), 3.93 (1H, d, ² J_(HH) =15Hz, C3-H), 3.9 (2H, m, NCH₂ CH₂), 2.65 (2H, m, CH₂ CO₂), 1.25 (3H, t, ³J_(HH) =7 Hz, OCH₂ CH₃)

e) To a magnetically stirred solution of1-(4-iodophenyl)-4-(N-Boc)-piperzine (0.5 grams, 1.29 mmol) in 0.65 mLTHF at -78° C. under an atmosphere of nitrogen was added n-BuLi as a2.5M solution in hexane (1.42 mmol, 1.1 molar equiv., 0.57 mL) over a 5minute period. The mixture was stirred for 15 minutes at -78° C. and thetreated with triisopropylborate (3 molar equiv., 3.9 mmol, 0.9 mL). Themixture was allowed to warm to room temperature and stirred overnight(ca. 12 hours). The mixture was cooled to 0° C. and acidified to pH 6.5with 5% aq. HCl and extracted with CH₂ Cl₂ (50 mL). The organic layerwas washed with brine, dried over sodium sulfate, decanted andconcentrated in vacuo. The resulting residue, in a minimum volumn ofethanol, was added to a prestirred (10 mins) mixture oftetrakistriphenylphosphine palladium (0.03 molar equiv., 0.026 mmol, 30mgs), and 0.447 grams of1-(p-chlorobenzyl)-7-iodo-4-(2-carboxyethyl)-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dioneethyl ester (0.85 mmol) in 0.5 mL dimethylformamide at room temperature.1.3 mL of a 2M solution of sodium carbonate (2 equiv.) was added and thereaction mixture heated to 80° C. for 6 hours. The mixture was allowedto cool to room temperature and is quenched with 1N HCl (25 mL) andextracted 3×50 mL ethyl acetate. The combined organics were washed 1×50mL sat NaHCO₃, brine, dried over Na₂ SO₄, decanted and concentrated invacuo. The resulting residue was chromatographed (SiO₂, 1:1 EtOAc/hexaneto 9:1 EtOAc/hexane as the eluting solvent) to yield1-(p-chlorobenzyl)-7-[4-(4-N-Boc-1-piperazine)phenyl]-4-(2-carboxyethyl)-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dioneethyl ester (0.137 grams, 24%, R_(f) (SiO₂, 1:1 EtOAc/hexane)=0.15, muand ninhydrin positive). ¹ H NMR (CDCl₃, dTMS) 8.00 (1H, d, ⁴ J_(HH) =2Hz, C6-H), 7.59 (1H, dd, ⁴ J_(HH) =2 Hz, ³ J_(HH) =9 Hz, C8-H), 7.50(2H, d, ³ J_(HH) =9 Hz, C7 -o-ArH), 7.23 (2H, d, ³ J_(HH) =8 Hz, CH₂-m-ArH), 7.16 (1H, d, ³ J_(HH) =9 Hz, C9-H), 7.10 (2H, d, ³ J_(HH) =9Hz, CH₂ -o-ArH), 6.95 (2H, d, ³ J_(HH) =8 Hz, C7-m-ArH), 5.08 (1H, d, ²J_(HH) =16 Hz, NCHHAr), 4.99 (1H, d, ² J_(HH) =16 Hz, NCHHAr), 4.18 (1H,d, ² J_(HH) =15 Hz, C3-H), 4.13 (2H, q, ³ J_(HH) =7 Hz, OCH₂), 3.92 (2H,m, NCH₂ CH₂), 3.92 (1H, d, ² J_(HH) =15 Hz, C3-H), 3,58 (4H, t, ³ J_(HH)=5 Hz, NCH₂ CH₂ NH), 3.18 (4H, t, ³ J_(HH) =5 Hz, NCH₂ NCH₂ NH), 2.68(2H, m, CH₂ CO₂), 1.47 (9H, s, Bu^(t)), 1.25 (3H, t, ³ J_(HH) =7 Hz).13C NMR 171.3, 168.5, 167.1, 154.7, 150.9, 138.6, 138.0, 135.2, 133.3,132.1, 130.9, 129.9, 129.7, 128.9, 128.4, 127.5, 121.9, 116.4, 79.9,60.8, 52.4, 50.6, 48.8, 45.1, 32.8, 28.4, 14.2.

Using the above procedure, but substituting the appropriate7-iodo-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dione alkyl ester for1-(p-chlorobenzyl)-7-iodo-4-(2-carboxyethyl)-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dioneethyl ester and substituting the appropriate iodoarene for1-(4-iodophenyl)-4-(N-Boc)-piperzine there may be prepared, for example,the following compounds:

1-methyl-7-[4-(4-N-Boc-1-piperazine)phenyl]-4-(2-carboxyethyl)-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dioneethyl ester,

1-(diphenylmethyl)-7-[4-(4-N-Boc-1-piperazine)phenyl]-4-(2-carboxyethyl)-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dioneethyl ester,

1-(2-napthyl)methyl-7-[4-(4-N-Boc-1-piperazine)phenyl]-4-(2-carboxyethyl)-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dioneethyl ester,

(±)-1-methyl-7-[4-(4-N-Boc-1-piperazine)phenyl]-4-(3-phenyl-3-proprionate)-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dionemethyl ester,

(±)-1-(2-napthyl)methyl-7-[4-(4-N-Boc-1-piperazine)phenyl]-4-(3-phenyl-3-proprionate)-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dionemethyl ester,

1-(p-chlorobenzyl)-7-[4-(2-(N-Boc)-aminoethoxy)phenyl]-4-(2-carboxyethyl)-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dioneethyl ester

1-methyl-7-[4-(2-(N-Boc)-aminoethoxy)phenyl]-4-(2-carboxyethyl)-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dioneethyl ester,

1-(diphenylmethyl)-7-[4-(2-(N-Boc)-aminoethoxy)phenyl]-4-(2-carboxyethyl)-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dioneethyl ester,

1-(2-napthyl)methyl-7-[4-(2-(N-Boc)-aminoethoxy)phenyl]-4-(2-carboxyethyl)-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dioneethyl ester,

(±)-1-methyl-7-[4-(2-(N-Boc)-aminoethoxy)phenyl]-4-(3-phenyl-3-proprionate)-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dionemethyl ester,

(±)-1-(2-napthyl)methyl-7-[4-(2-(N-Boc)-aminoethoxy)phenyl]-4-(3-phenyl-3-proprionate)-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dionemethyl ester,

1-(p-chlorobenzyl)-7-[4-(N-Boc-aminomethyl)phenyl]-4-(2-carboxyethyl)-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dioneethyl ester

1-methyl-7-[4-(N-Boc-aminomethyl)phenyl]-4-(2-carboxyethyl)-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dioneethyl ester,

1-(diphenylmethyl)-7-4-(N-Boc-aminomethyl)phenyl]-4-(2-carboxyethyl)-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dioneethyl ester,

1-(2-napthyl)methyl-7-[4-(N-Boc-aminomethyl)phenyl]-4-(2-carboxyethyl)-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dioneethyl ester,

(±)-1-methyl-7-[4-(N-Boc-aminomethyl)phenyl]-4-(3-phenyl-3-proprionate)-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dionemethyl ester,

(±)-1-(2-napthyl)methyl-7-[4-(N-Boc-aminomethyl)phenyl]-4-(3-phenyl-3-proprionate)-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dionemethyl ester.

f)1-(p-chlorobenzyl)-7-[4-(1-piperazine)phenyl]-4-(2-carboxyethyl)-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dionetrifluoroacetate was prepared using the method described in part (c) ofexample 1. Thus, 34 mgs (0.052 mmol)1-(p-chlorobenzyl)-7-[4-(4-N-Boc-1-piperazine)phenyl]-4-(2-carboxyethyl)-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dioneethyl ester yielded 25 mgs (90%) of1-(p-chlorobenzyl)-7-[4-(1-piperazine)phenyl]-4-(2-carboxyethyl)-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dionetrifluoroacetate (1/2" C-18 reverse-phase column, eluting with a solventgradient of 1:9 acetonitrile(0.1% TFA)/water (0.1% TFA) time 0 to 10minutes, to 1:1 acetonitrile(0.1% TFA)/water (0.1% TFA) time 10 to 40minutes, flow 10 mL/min, R_(t) =34.9 min, mu detection 254 nM). HRMS(FAB) molecular ion m/z=533.1950 (cald. C29H30N4O4Cl, 533.1956). ¹ H NMR(D₂ O,10%CD₃ OD) 7.61 (1H, d, ⁴ J_(HH) =2 Hz, C6-H), 7.43 (1H, dd, ⁴J_(HH) =2 Hz, ³ J_(HH) =8 Hz, C8-H), 7.28 (2H, d, C7-o-ArH), 7.10 (1H,d, ³ J_(HH) =8 Hz, C9-H), 6.98 (2H, d, ³ J_(HH) =7 Hz, CH₂ -m-ArH), 6.87(2H, d, ³ J_(HH) =7 Hz, CH₂ -o-ArH), 6.80 (2H, d, ³ J_(HH) =8 Hz,C7-m-ArH), 5.20 (1H, d, ² J_(HH) =16 Hz, NCHHAr), 3.95 (1H, d, ² J_(HH)=14 Hz, C3-H), 3.84 (1H, dt, NCHHCH.sub. 2), 3.72 (1H, d, ² J_(HH) =14Hz, C3-H), 3.58 (1H, dt, C3-H), 3.23 (4H, bs, NCH₂ CH₂ NH), 3.18 (4H,bs, NCH₂ CH₂ NH), 2.58 (2H, t, 3JHH=7 Hz, CH₂ CO₂).

Using the above procedure, but substituting the appropriate7-aryl-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dione N-Boc amine alkylester for1-(p-chlorobenzyl)-7-[4-(4-N-Boc-1piperazine)phenyl]-4-(2-carboxyethyl)-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dioneethyl ester there may be prepared, for example, the following compounds:

1-methyl-7-[4-(1-piperazine)phenyl]-4-(2-carboxyethyl)-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dionetrifluoroacetate,

1-(diphenylmethyl)-7-[4-(1-piperazine)phenyl]-4-(2-carboxyethyl)-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dionetrifluoroacetate,

1-(2-napthyl)methyl-7-[4-(1-piperazine)phenyl]-4-(2-carboxyethyl)-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dionetrifluoroacetate,

(±)-1-methyl-7-[4-(1-piperazine)phenyl]-4-(3-phenyl-3-proprionate)-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dionetrifluoroacetate,

(±)-1-(2-napthyl)methyl-7-[4-(1-piperazine)phenyl]-4-(3-phenyl-3-proprionate)-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dionetrifluoroacetate,

1-(p-chlorobenzyl)-7-[4-(2-aminoethoxy)phenyl]-4-(2-carboxyethyl)-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dionetrifluoroacetate,

1-methyl-7-[4-(2-aminoethoxy)phenyl]-4-(2-carboxyethyl)-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dionetrifluoroacetate,

1-(diphenylmethyl)-7-[4-(2-aminoethoxy)phenyl]-4-(2-carboxyethyl)-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dionetrifluoroacetate,

1-(2-napthyl)methyl-7-[4-(2-aminoethoxy)phenyl]-4-(2-carboxyethyl)-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dionetrifluoroacetate,

(±)-1-methyl-7-[4-(2-aminoethoxy)phenyl]-4-(3-phenyl-3-proprionate)-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dionetrifluoroacetate,

(±)-1-(2-napthyl)methyl-7-[4-(2-aminoethoxy)phenyl]-4-(3-phenyl-3-proprionate)-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dionetrifluoroacetate,

1-(p-chlorobenzyl)-7-[4-(aminomethyl)phenyl]-4-(2-carboxyethyl)-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dionetrifluoroacetate,

1-methyl-7-[4-(aminomethyl)phenyl]-4-(2-carboxyethyl)-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dionetrifluoroacetate,

1-(diphenylmethyl)-7-4-(aminomethyl)phenyl]-4-(2-carboxyethyl)-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dionetrifluoroacetate,

1-(2-napthyl)methyl-7-[4-(aminomethyl)phenyl]-4-(2-carboxyethyl)-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dionetrifluoroacetate,

(±)-1-methyl-7-[4-(aminomethyl)phenyl]-4-(3-phenyl-3-proprionate)-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dionetrifluoroacetate,

(±)-1-(2-napthyl)methyl-7-[4-(aminomethyl)phenyl]-4-(3-phenyl-3-proprionate)-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dionetrifluoroacetate.

EXAMPLE 13 ##STR47##1-[3-(N-(4-aminobuturyl))aminophenyl]methyl-4-(2-carboxyethyl)-7-(6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dionebistrifluoroacetate

a)1-(3-nitrophenyl)methyl-4-(2-carboxyethyl)-7-(N-Boc-6-aminohexynyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dioneethyl ester (110 mgs, 0.18 mmol) was reduced under an atmosphere ofnitrogen in 4 mL ethyl acetate in the presence of a catalytic amount of10% Pd on carbon (25 mgs), monitoring the reaction by TLC (SiO₂, 1:1ethyl acetate/hexane, R_(f) (starting material)=0.33, R_(f)(product)=0.15, mu and ninhydrin positive). After 3 hours, the reactionwas filtered through Celite®, washing with ethyl acetate, andconcentrated in vacuo to yield 97 mgs (92%) of1-(3-aminophenyl)methyl-4-(2-carboxyethyl)-7-(N-Boc-6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dioneethyl ester. 1H NMR (CDCl₃, dTMS) 7.58 (1H, d, ⁴ J_(HH) =2 Hz, C6-H),7.18 (1H, dd, ⁴ J_(HH) =2 Hz, ³ J_(HH) =8 Hz, C8-H), 7.09 (1H, d, ³J_(HH) =9 Hz, CH₂ ArH), 7.04 (1H, t, 3JHH=8 Hz, CH₂ ArH), 6.54 (1H, bd,CH₂ ArH), 6.48 (1H, bs, CH₂ ArH), 4.99 (1H, d, ² J_(HH) =16 Hz, CHHAr),4.90 (1H, d, 2JHH=16 Hz, CHHAr), 4.53 (1H, vbs, NHBoc), 4.20-3.96 (4H,m, OCH₂, C3-H, NCHHCH₂), 3.92-3.80 (2H, m, C3-H, NCHHCH₂), 3.55 (2H, bs,NH₂), 3.06 (2H, bq, ³ J_(HH) =6 Hz, CH₂ NHBoc), 2.72 (2H, m, CH₂ CO₂),2.56 (2H, t, ³ J_(HH) =7 Hz), 1.66-1.20 (20H, m, (CH₂)₄, Bu^(t), OCH₂CH₃). 13C NMR (CDCl3) 171.4, 168.5, 167.4, 146.3, 140.7, 138.1, 137.9,132.2, 130.1, 129.6, 129.0, 121.6, 117.4, 114.5, 113.6, 79.0, 60.8,52.4, 51.1, 45.1, 40.5, 34.9, 32.8, 30.8, 29.9, 28.8, 28.4, 26.5, 14.2.

Using the above procedure, but substituting the appropriate 7-alkyl oraryl-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dione N-Boc amino alkyl esterfor1-(3-nitrophenyl)methyl-4-(2-carboxyethyl)-7-(N-Boc-6-aminohexynyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dioneethyl ester there may be prepared, for example, the following compounds:

1-(2-aminophenyl)methyl-4-(2-carboxyethyl)-7-(N-Boc-6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dioneethyl ester,

1-(4-aminophenyl)methyl-4-(2-carboxyethyl)-7-(N-Boc-6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dioneethyl ester,

1-(3-aminophenyl)methyl-4-(2-carboxyethyl)-7-[4-(4-N-Boc-1-piperazine)phenyl]-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dioneethyl ester,

1-(3-aminophenyl)methyl-4-(3-phenyl-3-proprionate)-7-[4-(4-N-Boc-1-piperazine)phenyl]-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dioneethyl ester,

1-(3-aminophenyl)methyl-4-(3-phenyl-3-proprionate)-7-[4-(4-N-Boc-1-piperazine)phenyl]-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dioneethyl ester,

1-(3-aminophenyl)methyl-4-(3-phenyl-3-proprionate)-7-(N-Boc-6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dioneethyl ester,

b) A solution of the aniline1-(3-aminophenyl)methyl-4-(2-carboxyethyl)-7-(N-Boc-6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dioneethyl ester (50 mgs, 0.09 mmol) and 0.5 mL dimethylacetamide was addedto a prestirred solution of N-Boc-4-aminobutyric acid (0.16 mmol, 32.5mgs), 0.5 mL dimethylacetamide, 0.5 mL pyridine, andbenztriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate(BOP Reagent) and a catalytic amount of dimethylaminopyridine (DMAP, 5mgs), monitoring by TLC (8:2 ethyl acetate/hexane). After 6 hours, thereaction was poured over 50 mL 1N HCl and extracted 2×50 mL ethylacetate. The combined organics was dried over sodium sulfate, decanted,and concentrated in vacuo. The resulting residue was purified by columnchromatography, SiO₂, using 7:3 ethyl acetate/hexane to 9:1 ethylacetate/hexane, R_(f) (8:2 ethyl acetae/hexane, product)=0.15, to yield59 mgs (86%) of1-[3-(4-N-Boc-aminobutyryl)aminophenyl]methyl-4-(2-carboxyethyl)-7-(N-Boc-6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dioneethyl ester. ¹ H NMR (CDCl₃, dTMS) 8.78 (1H, bs, ArNHCO), 7.56 (1H, d, ⁴J_(HH) =2 Hz, C6-H), 7.44 (1H, bd, ³ J_(HH) =8 Hz, C8-H), 7.36 (1H, bs,CH₂ ArH), 7.17 (2H, m, CH₂ ArH), 7.09 (1H, t, ³ J_(HH) =8 Hz, CH₂ ArH),6.81 (1H, bd, ³ J_(HH) =8 Hz, C9-H), 5.1-4.9 (3H, m, NHBoc, CH₂ Ar),4.58 (1H, bs, NHBoc), 4.20-4.05 (4H, m, OCH₂, C3-H, NCHHCH₂), 3.87 (1H,d, ² J_(HH) =15 Hz, C3-H), 3.80 (1H, dt, NCHHCH₂), 3.16 (2H, bq, ³J_(HH) =6 Hz, CH₂ NHBoc), 3.04 (2H, bq, ³ J_(HH) =6 Hz, CH₂ NHBoc), 2.71(2H, m, CH₂ CO₂), 2.54 (2H, t, ³ J_(HH) =7 Hz, NCOCH₂), 2.32 (2H, t, ³J_(HH) =7 Hz, ArCH₂), 1.82 (2H, p, ³ J_(HH) =7 Hz, NCOCH₂ CH₂), 1.6-1.2(20H, m, (CH₂)₄, Bu^(t), OCH₂ CH₃).

Using the above procedure, but substituting the appropriate 7-alkyl oraryl-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dione N-Boc amino alkyl esterfor1-(3-aminophenyl)methyl-4-(2-carboxyethyl)-7-(N-Boc-6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dioneethyl ester there may be prepared, for example, the following compounds:

1-[2-(4-N-Boc-aminobutyryl)aminophenyl]methyl-4-(2-carboxyethyl)-7-(N-Boc-6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dioneethyl ester,

1-(4-(4-N-Boc-aminobutyryl)aminophenyl)methyl-4-(2-carboxyethyl)-7-(N-Boc-6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dioneethyl ester,

1-(3-(4-N-Boc-aminobutyryl)aminophenyl)methyl-4-(2-carboxyethyl)-7-[4-(4-N-Boc-1-piperazine)phenyl]-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dioneethyl ester,

1-(3-(4-N-Boc-aminobutyryl)aminophenyl)methyl-4-(3-phenyl-3-proprionate)-7-[4-(4-N-Boc-1-piperazine)phenyl]-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dioneethyl ester,

1-(3-(4-N-Boc-aminobutyryl)aminophenyl)methyl-4-(3-phenyl-3-proprionate)-7-(N-Boc-6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dioneethyl ester,

1-[3-(3-N-Boc-aminopropionyl)aminophenyl]methyl-4-(2-carboxyethyl)-7-(N-Boc-6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dioneethyl ester,

1-[2-(3-N-Boc-aminopropionyl)aminophenyl]methyl-4-(2-carboxyethyl)-7-(N-Boc-6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dioneethyl ester,

1-(4-(3-N-Boc-aminopropionyl)aminophenyl)methyl-4-(2-carboxyethyl)-7-(N-Boc-6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dioneethyl ester,

1-(3-(3-N-Boc-aminopropionyl)aminophenyl)methyl-4-(2-carboxyethyl)-7-[4-(4-N-Boc-1-piperazine)phenyl]-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dioneethyl ester,

1-(3-(3-N-Boc-aminopropionyl)aminophenyl)methyl-4-(3-phenyl-3-proprionate)-7-[4-(4-N-Boc-1-piperazine)phenyl]-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dioneethyl ester,

1-(3-(3-N-Boc-aminopropionyl)aminophenyl)methyl-4-(3-phenyl-3-proprionate)-7-(N-Boc-6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dioneethyl ester.

c)1-[3-(N-(4-aminobuturyl))aminophenyl]methyl-4-(2-carboxyethyl)-7-(6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dionetrifluoroacetate was prepared using the method described in part (c) ofexample 1. Thus, 59 mgs (0.074 mmol)1-[3-(4-N-Boc-aminobutyryl)aminophenyl]methyl-4-(2-carboxyethyl)-7-(N-Boc-6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dioneethyl ester yielded 50 mgs (99%) of1-[3-(N-(4-aminobuturyl))aminophenyl]methyl-4-(2-carboxyethyl)-7-(6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dionetrifluoroacetate (1/2" C-18 reverse-phase column, eluting with a solventgradient of 1:9 acetonitrile(0.1% TFA)/water (0.1% TFA) time 0 to 10minutes, to 1:1 acetonitrile(0.1% TFA)/water (0.1% TFA) time 10 to 40minutes, flow 10 mL/min, R_(t) =30.5 min, mu detection 254 nM). HRMS(FAB) molecular ion m/z=538.3032 (cald. C₂₉ H₃₉ N₅ O₅, 538.3030). ¹ HNMR (D₂ O) 7.21 (1H, bs, C6-H), 7.05-6.85 (5H, m, CH₂ ArH, C8-H), 6.52(1H, bd, ³ J_(HH) =8 Hz, C9-H), 5.03 (1H, d, ² J_(HH) =16 Hz, CHHAr),4.47 (1H, d, ² J_(HH) =16 Hz, CHHAr), 3.86 (1H, d, ² J_(HH) =15 Hz,C3-H), 3.80 (1H, dt, ³ J_(HH) =7 Hz, ² J_(HH) =15 Hz, NCHHCH₂), 3.63(1H, d, ² J_(HH) =15 Hz, C3-H), 3.51 (1H, dt, ³ J_(HH) =7 Hz, ² J_(HH)=15 Hz, NCHHCH₂), 2.83 (2H, t, ³ J_(HH) =8 Hz, CH₂ NH₂), 2.68 (2H, t, ³J_(HH) =8 Hz, CH₂ NH₂), 2.43 (2H, t, ³ J_(HH) =7 Hz), 2.3-2.2 (4H, m),1.76 (2H, p, ³ J_(HH) =7 Hz, NCOCH₂ CH₂), 1.35 (2H, p, ³ J_(HH) =7 Hz),1.22 (2H, p, ³ J_(HH) =7 Hz), 1.1-0.9 (4H, m).

Using the above procedure, but substituting the appropriate 7-alkyl oraryl-3,4-dihydro-1H-1,4-benzodiazpine-2,4-dione bis-N-Boc diamino alkylester for1-[3-(4-N-Boc-aminobutyryl)aminophenyl]methyl-4-(2-carboxyethyl)-7-(N-Boc-6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dioneethyl ester there may be prepared, for example, the following compounds:

1-[2-(4-aminobutyryl)aminophenyl]methyl-4-(2-carboxyethyl)-7-(6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dionebistrifluoroacetate,

1-(4-(4-aminobutyryl)aminophenyl)methyl-4-(2-carboxyethyl)-7-(6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dionebistrifluoroacetate,

1-(3-(4-aminobutyryl)aminophenyl)methyl-4-(2-carboxyethyl)-7-[4-(1-piperazine)phenyl]-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dionebistrifluoroacetate,

1-(3-(4-aminobutyryl)aminophenyl)methyl-4-(3-phenyl-3-proprionate)-7-[4-(1-piperazine)phenyl]-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dionebistrifluoroacetate,

1-(3-(4-aminobutyryl)aminophenyl)methyl-4-(3-phenyl-3-proprionate)-7-(6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dionebistrifluoroacetate,

1-[3-(3-aminopropionyl)aminophenyl]methyl-4-(2-carboxyethyl)-7-(6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dionebistrifluoroacetate,

1-[2-(3-aminopropionyl)aminophenyl]methyl-4-(2-carboxyethyl)-7-(6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dionebistrifluoroacetate,

1-(4-(3-aminopropionyl)aminophenyl)methyl-4-(2-carboxyethyl)-7-(6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dionebistrifluoroacetate,

1-(3-(3-aminopropionyl)aminophenyl)methyl-4-(2-carboxyethyl)-7-[4-(1-piperazine)phenyl]-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dionebistrifluoroacetate,

1-(3-(3-aminopropionyl)aminophenyl)methyl-4-(3-phenyl-3-proprionate)-7-[4-(4-(1-piperazine)phenyl]-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dionebistrifluoroacetate,1-(3-(3-aminopropionyl)aminophenyl)methyl-4-(3-phenyl-3-proprionate)-7-(6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazapine-2,5-dionebistrifluoroacetate.

EXAMPLE 14 ##STR48##1-(diphenylmethyl)-4-(2-carboxyethyl)-7-(5-aminopentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate

a) A magnetically stirred solution of 1.1 gram ofN-(2-amino-5-iodobenzoyl)-b-alanine ethyl ester (3.1 mmol), prepared bythe method shown in part (b) of example 1, 0.48 mL of 2,6-lutidine (4.1mmol), 1.2 grams of chlorodiphenylmethane (4.7 mmol), and 10 mL ofdimethylformamide was heated to 50° C. for 1 hour. The reaction mixturewas allowed to cool to room temperature and concentrated in vacuo. Theresulting oil was dissolved in 35 mL of methylene chloride and washedwith 2×50 mL 10% citric acid, 1×50 mL water, dried over sodium sulfate,decanted and concentrated in vacuo. The resulting oil was furtherpurified by column chromatography, using silica gel, eluting with asolvent gradient of 10/90 ethyl acetate/hexane to 25/75 ethylacetate/hexane (TLC, SiO₂, 1:1 EtOAc/hexane, R_(f) =0.82, υν positive)to yield 0.92 gram (56%) ofN-(2-diphenylmethylamino-5-iodobenzoyl)-b-alanine ethyl ester. ¹ H NMR(CDCl₃, dTMS) 8.40 (1H, d, ³ J_(HH) =5 Hz, NHCHAr₂), 7.56 (1H, d, ³J_(HH) =2 Hz, ArH o-CON), 7.18-7.36 (1H, m, ⁴ J_(HH) =2 Hz, ArH Ph, ArHp-CON), 6.73 (1H, t, ³ J_(HH) =6 Hz, NHCH₂), 6.29 (1H, d, ³ J_(HH) =9Hz, ArH m-CON), 5.52 (1H, d, ³ J_(HH) =5 Hz, CHNH), 4.15 (2H, q, ³J_(HH) =7 Hz, OCH₂), 3.61 (2H, q, ³ J_(HH) =6 Hz, CH₂ NH), 2.58 (2H, t,³ J_(HH) =6 Hz, CH₂ CO), 1.25 (3H, t, ³ J_(HH) =6 Hz, CH₃ CH₂ O).

Using the above procedure, but substituting the appropriate alkyl oraryl halide there may be prepared, for example, the following compounds:

N-(2-(1-napthyl)methylamino-5-iodobenzoyl)-b-alanine ethyl ester,

N-(2-(2-napthyl)methylamino-5-iodobenzoyl)-b-alanine ethyl ester,

N-(2-(p-phenoxybenzyl)amino-5-iodobenzoyl)-b-alanine ethyl ester,

N-(2-(m-phenoxybenzyl)amino-5-iodobenzoyl)-b-alanine ethyl ester,

N-(2-(p-trifluoromethylbenzyl)amino-5-iodobenzoyl)-b-alanine ethylester,

N-(2-(ethyl-5-valeroyl)amino-5-iodobenzoyl)-b-alanine ethyl ester,

N-(2-(p-methoxybenzyl)amino-5-iodobenzoyl)-b-alanine ethyl ester,

Methyl3(S)-N-(2-(2-methylnaphthyl)amino-5-iodobenzoyl)-3-amino-3-methylpropionate,

Methyl3(R)-N-(2-(2-napthyl)methylamino-5-iodobenzoyl)-3-amino-3-methylpropionate

Methyl(+/-)-N-(2-(2-napthyl)methylamino-5-iodobenzoyl)-3-amino-3-methylpropionate,

Methyl3(S)-N-(2-(2-napthyl)methylamino-5-iodobenzoyl)-3-amino-3-phenylpropionate

Methyl3(R)-N-(2-(2-napthyl)methylamino-5-iodobenzoyl)-3-amino-3-phenylpropionate

Methyl(+/-)-N-(2-(2-napthyl)methylamino-5-iodobenzoyl)-3-amino-3-phenylpropionate,

b) To a magnetically stirred solution of 0.93 gram ofN-(2-diphenylmethlamino-5-iodobenzoyl)-b-alanine ethyl ester (1.8 mmol)in 15 mL of methylene chloride and 15 mL water, was added 183 mLa-bromoacetylbromide (2.1 mmol). The reaction mixture was stirredovernight. The layers were separated, the aqueous fraction was washed1×15 mL methylene chloride, and the two methylene chloride fractionswere combined and washed with 1×20 mL of saturated sodium bicarbonate,dried over sodium sulfate, filtered and concentrated in vacuo. Theresulting residue was dissolved in 7 mL of dimethylformamide and added,via an addition funnel, to a slurry of 57 mgs of 95% sodium hydride (2.2mmol) in 5 mL dimethylformamide that was cooled at 0° C. After 2 hours,the mixture was poured over 40 mL of ice cooled 10% citric acid andextracted 3×40 mL methylene chloride. The combined organic layers werewashed with 2×50 mL of 10% citric acid and 1×50 mL water, dried oversodium sulfate, decanted, concentrated in vacuo and further purified bycolumn chromatography, using silica gel, eluting with a 1:1 mixture ofethyl acetate and hexane (TLC, SiO₂, 1:1 EtOAc/hexane, R_(f) =0.61, υνpositive) to yield 474 mgs (48%) of1-(diphenylmethyl)-4-(2-carboxyethyl)-8-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester. ¹ H NMR (CDCl₃, dTMS) 8.03 (1H, d, ³ J_(HH) =2 Hz, ArHo-CON), 7.45 (1H, dd, ³ J_(HH) =2 Hz, ³ J_(HH) =9 Hz, ArH p-CON),7.1-7.4 (1H, m, ⁴ J_(HH) =2 Hz, ArH Ph), 6.79 (1H, d, ³ J_(HH) =9 Hz,ArH m-CON), 6.70 (1H, s), 4.13 (2H, q, ³ J_(HH) =7 Hz, OCH₂), 3.98 (2H,dd, ³ J_(HH) =100 Hz, ³ J_(HH) =15 Hz, COCH₂ N), 3.86 (2H, dm, ³ J_(HH)=62 Hz, ³ J_(HH) =8 Hz, CH₂ N), 2.58 (2H, dm, ³ J_(HH) =40 Hz, ³ J_(HH)=8 Hz, CH₂ CO), 1.27 (3H, t, ³ J_(HH) =7 Hz, CH₃ CH₂ O). ¹³ C NMR(CDCl₃) 171.2, 168.0, 165.6, 139.9, 139.3, 138.8, 138.1, 137.5, 132.0,129.1, 128.5, 128.4, 128.0, 128.0, 128.0, 127.9, 127.6, 125.4, 90.6,67.2, 60.8, 53.1, 45.0, 32.6, 14.2.

Using the above procedure, but substituting the appropriateN-(2-amino-5-iodobenzoyl)-b-alanine ethyl ester forN-(2-diphenylmethylamino-5-iodobenzoyl)-b-alanine ethyl ester there maybe prepared, for example, the following compounds:

1-(1-napthyl)methyl-4-(2-carboxyethyl)-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester,

1-(2-napthyl)methyl-4-(2-carboxyethyl)-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester,

1-(m-phenoxybenzyl)-4-(2-carboxyethyl)-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester,

1-(p-phenoxybenzyl)-4-(2-carboxyethyl)-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester,

1-(p-trifluoromethylbenzyl)-4-(2-carboxyethyl)-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester,

1-(ethyl-5-valeroyl)-4-(2-carboxyethyl)-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester,

1-(p-methoxybenzyl)-4-(2-carboxyethyl)-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester,

1-(p-methylmethylbenzoyl)-4-(2-carboxyethyl)-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester,

1-(2-napthyl)methyl-4-(3(S)-butanoate)-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionemethyl ester,

1-(2-napthyl)methyl-4-(3(R)-butanoate)-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionemethyl ester,

1-(2-napthyl)methyl-4-((+/-)3-butanoate)-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionemethyl ester,

1-(2-napthyl)methyl-4-(3(S)-phenyl-3-proprionate)-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionemethyl ester,

1-(2-napthyl)methyl-4-(3(R)-phenyl-3-proprionate)-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionemethyl ester,

1-(2-napthyl)methyl-4-((+/-)3-phenyl-3-proprionate)-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionemethyl ester.

c) To a magnetically stirred solution of 208 mgs of1-(diphenylmethyl)-4-(2-carboxyethyl)-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester (0.37 mmol) in 6 mL ethyl acetate, degassed of oxygen, underan atmosphere of nitrogen, was added 134 mgs of N-boc-5-amino-1-pentyne(0.74 mmol), prepared as described in part (e) of example 1, 10 mgs ofbistriphenylphosphine palladium dichloride (0.014 mmol), 5 mgs ofcuprous iodide (0.026 mmol) and 250 μL of triethylamine (1.75 mmol).After 1.5 hours, the reaction mixture was diluted with 35 mL of ethylacetate and washed with 1×15 mL 5% EDTA.Na₂, dried over sodium sulfate,decanted, concentrated in vacuo, and further purified by columnchromatography, using silica gel, eluting with a 1:1 mixture of ethylacetate and hexane (TLC, SiO₂, 1:1 EtOAc/hexane, R_(f) =0.46, υνpositive) to yield 131 mgs (60%) of 1-(diphenylmethyl)-4-(2-carboxyethyl)-8-(N-boc-5-amino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester. ¹ H NMR (CDCl₃, TMS) 7.71 (1H, d, ⁴ J_(HH) =2 Hz, ArHo-CON), 7.10-7.36 (11H, m, ³ J_(HH) =2 Hz, ArH Ph, ArH p-CON), 6.94 (1H,d, ⁴ J_(HH) =9 Hz, ArH p-CON), 6.67 (1H, s, CHAr₂), 4.78 (1H, s, NHBoc),4.10 (2H, q, ³ J_(HH) =7 Hz, CH₂ O) 3.95 (2H, dd, ² J_(HH) =106 Hz, ²J_(HH) =15 Hz, COCH₂ CN), 3.82 (2H, dm, ²,3 J_(HH) =7 Hz, ²,3 J_(HH) =59Hz, CH₂ N), 3.19 (2H, q, ³ J_(HH) =3 Hz, CH₂ NHBoc), 2.54 (2H, dm, ³J_(HH) =7 Hz, ³ J_(HH) =21 Hz, CH₂ CO), 2.37 (2H, t, ³ J_(HH) =7 Hz, CH₂CC), 1.71 (2H, m, ³ J_(HH) =7 Hz, CH₂ CH₂ CH₂), 1.38 (9H, s, Ch₃ Boc),1.22 (3H, t, ³ J_(HH) =7 Hz, CH₃ CH₂ O).

Using the above procedure, but substituting the appropriate7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione for1-(diphenylmethyl)-4-(2-carboxyethyl)-7-iodo-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester and alkyne for N-boc-5-amino-1-pentyne there may beprepared, for example, the following compounds:

1-(diphenylmethyl)-4-(2-carboxyethyl)-7-(N-boc-6-amino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester,

1-(diphenylmethyl)-4-(2-carboxyethyl)-7-(N-boc-4-amino-1-butynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester,

1-(1-napthyl)methyl-4-(2-carboxyethyl)-7-(N-boc-5-amino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester,

1-(1-napthyl)methyl-4-(2-carboxyethyl)-7-(N-boc-6-amino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester,

1-(2-napthyl)methyl-4-(2-carboxyethyl)-7-(N-boc-5-amino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester,

1-(2-napthyl)methyl-4-(2-carboxyethyl)-7-(N-boc-6-amino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester,

1-(p-phenoxybenzyl)-4-(2-carboxyethyl)-7-(N-boc-5-amino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester,

1-(p-phenoxybenzyl)-4-(2-carboxyethyl)-7-(N-boc-6-amino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester,

1-(m-phenoxybenzyl)-4-(2-carboxyethyl)-7-(N-boc-5-amino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester,

1-(m-phenoxybenzyl)-4-(2-carboxyethyl)-7-(N-boc-6-amino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester,

1-(p-trifluoromethylbenzyl)-4-(2-carboxyethyl)-7-(N-boc-5-amino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester,

1-(p-trifluoromethylbenzyl)-4-(2-carboxyethyl)-7-(N-boc-6-amino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester,

1-(ethyl-5-valeroyl)-4-(2-carboxyethyl)-7-(N-boc-5-amino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester,

1-(ethyl-5-valeroyl)-4-(2-carboxyethyl)-7-(N-boc-6-amino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester,

1-(p-methoxybenzyl)-4-(2-carboxyethyl)-7-(N-boc-5-amino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester,

1-(p-methoxybenzyl)-4-(2-carboxyethyl)-7-(N-boc-6-amino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester,

1-(p-methylmethylbenzoyl)-4-(2-carboxyethyl)-7-(N-boc-5-amino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester,

1-(p-methylmethylbenzoyl)-4-(2-carboxyethyl)-7-(N-boc-6-amino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester,

1-(2-napthyl)methyl-4-(3(S)-butanoate)-7-(N-boc-5-amino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionemethyl ester,

1-(2-napthyl)methyl-4-(3(S)-butanoate)-7-(N-boc-6-amino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionemethyl ester,

1-(2-napthyl)methyl-4-(3(R)-butanoate)-7-(N-boc-5-amino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionemethyl ester,

1-(2-napthyl)methyl-4-(3(R)-butanoate)-7-(N-boc-6-amino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionemethyl ester,

1-(2-napthyl)methyl-4-((+/-)3-butanoate)-7-(N-boc-5-amino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionemethyl ester,

1-(2-napthyl)methyl-4-((+/-)3-butanoate)-7-(N-boc-6-amino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionemethyl ester,

1-(2-napthyl)methyl-4-(3(S)-phenyl-3-proprionate)-7-(N-boc-5-amino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionemethyl ester,

1-(2-napthyl)methyl-4-(3(S)-phenyl-3-proprionate)-7-(N-boc-6-amino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionemethyl ester,

1-(2-napthyl)methyl-4-(3(R)-phenyl-3-proprionate)-7-(N-boc-5-amino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionemethyl ester,

1-(2-napthyl)methyl-4-(3(R)-phenyl-3-proprionate)-7-(N-boc-6-amino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionemethyl ester,

1-(2-napthyl)methyl-4-((+/-)3-phenyl-3-proprionate)-7-(N-boc-5-amino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionemethyl ester,

1-(2-napthyl)methyl-4-((+/-)3-phenyl-3-proprionate)-7-(N-boc-6-amino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionemethyl ester.

d) To a magnetically stirred solution of 66 mgs of1-(diphenylmethyl)-4-(2-carboxyethyl)-8-(N-boc-5-amino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester (0.11 mmol) in 2 mL ethyl acetate, covered with anatmosphere of hydrogen, was added 23 mgs of palladium/carbon catalyst.The mixture was stirred for 1 hr. before filtering the mixture throughCelite® and concentrating in vacuo to yield quantitative yield of1-(diphenylmethyl)-4-(2-carboxyethyl)-8-(N-boc-5-aminopentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester. ¹ H NMR (CDCl₃, dTMS) 7.54 (1H, d, ⁴ J_(HH) =2 Hz, Ar-Ho-CON), 6.90-7.38 (12H, m, ³ J_(HH) =2 Hz, Ar-H Ph, ArH p-CON, ArHm-CON), 6.54 (1H, s, NCHAr₂), 4.64 (1H, s, NHBoc), 4.12 (2H, q, ³ J_(HH)=7 Hz, CH₂ O) 3.97 (2H, dd, ² J_(HH) =129 Hz, ² J_(HH) =15 Hz, COCH₂CN), 3.82 (2H, dm, ²,3 J_(HH) =6 Hz, ²,3 J_(HH) =75 Hz, CH₂ N), 3.07(2H, q, ³ J_(HH) =3 Hz, CH₂ NHBoc), 2.55 (4H, dm, t, ³ J_(HH) =7 Hz, ³J_(HH) =30 Hz, ³ J_(HH) =7 Hz, CH₂ CO, CH₂ Ar), 1.3-1.6 (4H, m, m, ³J_(HH) =7 Hz, ³ J_(HH) =7 Hz, CH₂ CH₂ Ar, CH₂ CH₂ NHBoc), 1.1-1.3 (14H,s, m, t, ³ J_(HH) =7 Hz, ³ J_(HH) =7 Hz, CH₃ Boc, CH₂ CH₂ CH₂ NHBoc, CH₃CH₂).

Using the above procedure, but substituting the appropriate4-(2-carboxyethyl)-7-(N-boc-amino-1-alkynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester for1-(diphenylmethyl)-4-(2-carboxyethyl)-7-(N-boc-5-amino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester there may be prepared, for example, the following compounds:

1-(diphenylmethyl)-4-(2-carboxyethyl)-7-(N-boc-6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester,

1-(diphenylmethyl)-4-(2-carboxyethyl)-7-(N-boc-4-aminobutyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester,

1-(1-napthyl)methyl-4-(2-carboxyethyl)-7-(N-boc-5-aminopentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester,

1-(1-napthyl)methyl-4-(2-carboxyethyl)-7-(N-boc-6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester,

1-(2-napthyl)methyl-4-(2-carboxyethyl)-7-(N-boc-5-aminopentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester,

1-(2-napthyl)methyl-4-(2-carboxyethyl)-7-(N-boc-6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester,

1-(p-phenoxybenzyl)-4-(2-carboxyethyl)-7-(N-boc-5-aminopentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester,

1-(p-phenoxybenzyl)-4-(2-carboxyethyl)-7-(N-boc-6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester,

1-(m-phenoxybenzyl)-4-(2-carboxyethyl)-7-(N-boc-5-aminopentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester,

1-(m-phenoxybenzyl)-4-(2-carboxyethyl)-7-(N-boc-6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester,

1-(p-trifluoromethylbenzyl)-4-(2-carboxyethyl)-7-(N-boc-5-aminopentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester,

1-(p-trifluoromethylbenzyl)-4-(2-carboxyethyl)-7-(N-boc-6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione ethyl ester,

1-(ethyl-5-valeroyl)-4-(2-carboxyethyl)-7-(N-boc-5-aminopentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester,

1-(ethyl-5-valeroyl)-4-(2-carboxyethyl)-7-(N-boc-6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester,

1-(p-methoxybenzyl)-4-(2-carboxyethyl)-7-(N-boc-5-aminopentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester,

1-(p-methoxybenzyl)-4-(2-carboxyethyl)-7-(N-boc-6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester,

1-(p-methylmethylbenzoyl)-4-(2-carboxyethyl)-7-(N-boc-5-aminopentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione ethyl ester,

1-(p-methylmethylbenzoyl)-4-(2-carboxyethyl)-7-(N-boc-6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester,

1-(2-napthyl)methyl-4-(3(S)-butanoate)-7-(N-boc-5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionemethyl ester,

1-(2-napthyl)methyl-4-(3(S)-butanoate)-7-(N-boc-6-amino-1-hexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionemethyl ester,

1-(2-napthyl)methyl-4-(3(R)-butanoate)-7-(N-boc-5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionemethyl ester,

1-(2-napthyl)methyl-4-(3(R)-butanoate)-7-(N-boc-6-amino-1-hexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionemethyl ester,

1-(2-napthyl)methyl-4-((+/-)3-butanoate)-7-(N-boc-5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionemethyl ester,

1-(2-napthyl)methyl-4-((+/-)3-butanoate)-7-(N-boc-6-amino-1-hexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionemethyl ester,

1-(2-napthyl)methyl-4-(3(S)-phenyl-3-proprionate)-7-(N-boc-5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionemethyl ester,

1-(2-napthyl)methyl-4-(3(S)-phenyl-3-proprionate)-7-(N-boc-6-amino-1-hexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionemethyl ester,

1-(2-napthyl)methyl-4-(3(R)-phenyl-3-proprionate)-7-(N-boc-5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionemethyl ester,

1-(2-napthyl)methyl-4-(3(R)-phenyl-3-proprionate)-7-(N-boc-6-amino-1-hexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionemethyl ester,

1-(2-napthyl)methyl-4-((+/-)3-phenyl-3-proprionate)-7-(N-boc-5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionemethyl ester,

1-(2-napthyl)methyl-4-((+/-)3-phenyl-3-proprionate)-7-(N-boc-6-amino-1-hexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionemethyl ester.

e) To a solution of 33 mgs of1-(diphenylmethyl)-4-(2-carboxyethyl)-7-(N-boc-5-aminopentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester (0.05 mmol) in 2 mL ethyl acetate was added 0.4 mLtriethylsilane (2.5 mmol) and 6 mL of saturated HCl/ethyl acetate at 5°C. After 1 hour at 5° C. the mixture was concentrated in vacuo anddiluted with 2 mL of methanol. To the methanolic solution was added 2 mLof 2N sodium hydroxide. After 1 hour, the reaction was quenched with 1/2mL of acetic acid, concentrated in vacuo, diluted with 5 mL of methanoland water and purified by high pressure liquid chromatography, using a1/2" C-18 reverse phase column, eluting with a solvent gradient of 30:70methanol (0.1% trifluoroacetic acid)/water (0.1% trifluoroacetic acid),time 0 to 10 minutes, to 70:30 methanol (0.1% trifluoroaceticacid)/water (0.1% trifluoroacetic acid), time 10 minutes to 40 minutes,flow=10 mL/min. (R_(t) =37.5 min., υν detection 254 nm) to yield 14 mgs(46%) of1-(diphenylmethyl)-4-(2-carboxyethyl)-7-(5-aminopentyl)-3,4-dihydro-1H-1,4-benxodiazepine-2,5-dionetrifluoroacetate. HRMS (FAB) molecular ion m/z=500.2529 (calc. C₃₀ N₃ O₄H₃₃, 500.2549). ¹ H NMR (CDCl₃, TMS) 6.60-7.20 (13H, m, ³ J_(HH) =2 Hz,ArH Ph, ArH p-CON, ArH o-CON, ArH m-CON), 6.33 (1H, s, NCH-Ar₂), 3.65(2H, dd, ² J_(HH) =113 Hz, ² J_(HH) =15 Hz, COCH₂ CN), 3.50 (2H, dm, ²,3J_(HH) =7 Hz, ²,3 J_(HH) =59 Hz, CH₂ N), 2.66 (2H, t, ³ J_(HH) =8 Hz,CH₂ NH₂) 2.22-2.39 (4H, m, t, ³ J_(HH) =6 Hz, ³ J_(HH) =8 Hz, CH₂ CO,CH₂ Ar), 1.20-1.33 (4H, m, m, ³ J_(HH) =7 Hz, CH₂ CH₂ Ar, CH₂ CH₂ NH₂),1.00 (2H, m, ³ J_(HH) =7 Hz, CH₂ CH₂ CH₂ NH₂).

Using the above procedure, but substituting the appropriate3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione for1-(diphenylmethyl)-4-(2-carboxyethyl)-7-(N-boc-5-aminopentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dioneethyl ester there may be prepared, for example, the following compounds:

1-(diphenylmethyl)-4-(2-carboxyethyl)-7-(6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(diphenylmethyl)-4-(2-carboxyethyl)-7-(4-aminobutyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(1-napthyl)methyl-4-(2-carboxyethyl)-7-(5-aminopentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(1-napthyl)methyl-4-(2-carboxyethyl)-7-(6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-(2-carboxyethyl)-7-(5-aminopentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-(2-carboxyethyl)-7-(6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(p-phenoxybenzyl)-4-(2-carboxyethyl)-7-(5-aminopentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(p-phenoxybenzyl)-4-(2-carboxyethyl)-7-(6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(m-phenoxybenzyl)-4-(2-carboxyethyl)-7-(5-aminopentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(m-phenoxybenzyl)-4-(2-carboxyethyl)-7-(6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(p-trifluoromethylbenzyl)-4-(2-carboxyethyl)-7-(5-aminopentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(p-trifluoromethylbenzyl)-4-(2-carboxyethyl)-7-(6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(ethyl-5-valeroyl)-4-(2-carboxyethyl)-7-(5-aminopentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(ethyl-5-valeroyl)-4-(2-carboxyethyl)-7-(6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(p-methoxybenzyl)-4-(2-carboxyethyl)-7-(5-aminopentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(p-methoxybenzyl)-4-(2-carboxyethyl)-7-(6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(p-methylmethylbenzoyl)-4-(2-carboxyethyl)-7-(5-aminopentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(p-methylmethylbenzoyl)-4-(2-carboxyethyl)-7-(6-aminohexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(diphenylmethyl)-4-(2-carboxyethyl)-7-(6-amino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(diphenylmethyl)-4-(2-carboxyethyl)-7-(4-amino-1-butynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(1-napthyl)methyl-4-(2-carboxyethyl)-7-(5-amino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(1-napthyl)methyl-4-(2-carboxyethyl)-7-(6-amino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-(2-carboxyethyl)-7-(5-amino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-(2-carboxyethyl)-7-(6-amino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(p-phenoxybenzyl)-4-(2-carboxyethyl)-7-(5-amino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(p-phenoxybenzyl)-4-(2-carboxyethyl)-7-(6-amino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(m-phenoxybenzyl)-4-(2-carboxyethyl)-7-(5-amino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(m-phenoxybenzyl)-4-(2-carboxyethyl)-7-(6-amino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(p-trifluoromethylbenzyl)-4-(2-carboxyethyl)-7-(5-amino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(p-trifluoromethylbenzyl)-4-(2-carboxyethyl)-7-(6-amino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(ethyl-5-valeroyl)-4-(2-carboxyethyl)-7-(5-amino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(ethyl-5-valeroyl)-4-(2-carboxyethyl)-7-(6-amino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(p-methoxybenzyl)-4-(2-carboxyethyl)-7-(5-amino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(p-methoxybenzyl)-4-(2-carboxyethyl)-7-(6-amino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(p-methylmethylbenzoyl)-4-(2-carboxyethyl)-7-(5-amino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(p-methylmethylbenzoyl)-4-(2-carboxyethyl)-7-(6-amino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-(3(S)-butanoate)-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-(3(S)-butanoate)-7-(6-amino-1-hexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-(3(R)-butanoate)-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-(3(R)-butanoate)-7-(6-amino-1-hexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-((+/-)3-butanoate)-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-((+/-)3-butanoate)-7-(6-amino-1-hexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-(3(S)-phenyl-3-proprionate)-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-(3(S)-phenyl-3-proprionate)-7-(6-amino-1-hexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-(3(R)-phenyl-3-proprionate)-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-(3(R)-phenyl-3-proprionate)-7-(6-amino-1hexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-((+/-)3-phenyl-3-proprionate)-7-(5-amino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-((+/-)3-phenyl-3-proprionate)-7-(6-amino-1-hexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-(3(S)-butanoate)-7-(5-amino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-(3(S)-butanoate)-7-(6-amino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-(3(R)-butanoate)-7-(5-amino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-(3(R)-butanoate)-7-(6-amino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-((+/-)3-butanoate)-7-(5-amino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-((+/-)3-butanoate)-7-(6-amino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-(3(S)-phenyl-3-proprionate)-7-(5-amino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-(3(S)-phenyl-3-proprionate)-7-(6-amino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-(3(R)-phenyl-3-proprionate)-7-(5-amino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-(3(R)-phenyl-3-proprionate)-7-(6-amino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-((+/-)3-phenyl-3-proprionate)-7-(5-amino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-((+/-)3-phenyl-3-proprionate)-7-(6-amino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate.

EXAMPLE 15 ##STR49##1-(diphenylmethyl)-4-(2-carboxyethyl)-7-(5-guanidinopentyl)-3,4-dihydro-1H-1,4-benxodiazepine-2,5-dionetrifluoroacetate

a) To a solution of 11 mgs of1-(diphenylmethyl)-4-(2-carboxyethyl)-7-(5-aminopentyl)-3,4-dihydro-1H-1,4-benxodiazepine-2,5-dionetrifluoroacetate (0.02 mmol) in 2 mL of methanol was added 1 mL of 5%potassium bicarbonate and 17 mgs of aminoiminomethanesulfonic acid (0.12mmol). After 30 minutes, the reaction mixture was quenched with 0.5 mLof acetic acid and concentrated in vacuo. The resulting residue wasdiluted with 5 mL of water and methanol and purified by high pressureliquid chromatography, using a 1/2" C-18 reverse phase column, elutingwith a solvent gradient of 30:70 methanol (0.1% trifluoroaceticacid)/water (0.1% trifluoroacetic acid), time 0 to 10 minutes, to 70:30methanol (0.1% trifluoroacetic acid)/water (0.1% trifluoroacetic acid),time 10 minutes to 40 minutes, flow=10 mL/min. (R_(t) =40.5 min., υνdetection 254 nm) to yield 9.3 mg (71%) of1-(diphenylmethyl)-4-(2-carboxyethyl)-7-(5-guanidinopentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate. HRMS (FAB) molecular ion m/z=542.2750 (calc. C₃₁ N₅ O₄H₃₅, 542.2767). ¹ H NMR (CDCl₃, dTMS) 6.78-7.22 (13H, m, ³ J_(HH) =2 Hz,ArH Ph, ArH p-CON, ArH o-CON, ArH m-CON), 6.45 (1H, s, NCHAr₂), 3.83(2H, dd, ² J_(HH) =113 Hz, ² J_(HH) =15 Hz, COCH₂ CN), 3.65 (2H, dm, ²,3J_(HH) =7 Hz, ²,3 J_(HH) =59 Hz, CH₂ N), 2.85 (2H, t, ³ J_(HH) =8 Hz,CH₂ NH₂) 2.25-2.45 (4H, t, t, CH₂ CO, CH₂ Ar), 1.31 (4H, m, m, ³ J_(HH)=7 Hz, CH₂ CH₂ Ar, CH₂ CH₂ NH₂ ), 0.98 (2H, m, ³ J_(HH) =7 Hz, CH₂ CH₂CH₂ NH₂).

Using the above procedure, but substituting the appropriate amino acidfor1-(diphenylmethyl)-4-(2-carboxyethyl)-7-(5-aminopentyl)-3,4-dihydro-1H-1,4-benxodiazepine-2,5-dionetrifluoroacetate there may be prepared, for example, the followingcompounds:

1-(diphenylmethyl)-4-(2-carboxyethyl)-7-(6-guanidinohexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(diphenylmethyl)-4-(2-carboxyethyl)-7-(4-guanidinobutyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(1-napthyl)methyl-4-(2-carboxyethyl)-7-(5-guanidinopentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(1-napthyl)methyl-4-(2-carboxyethyl)-7-(6-guanidinohexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-(2-carboxyethyl)-7-(5-guanidinopentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-(2-carboxyethyl)-7-(6-guanidinohexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(p-phenoxybenzyl)-4-(2-carboxyethyl)-7-(5-guanidinopentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(p-phenoxybenzyl)-4-(2-carboxyethyl)-7-(6-guanidinohexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(m-phenoxybenzyl)-4-(2-carboxyethyl)-7-(5-guanidinopentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(m-phenoxybenzyl)-4-(2-carboxyethyl)-7-(6-guanidinohexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(p-trifluoromethylbenzyl)-4-(2-carboxyethyl)-7-(5-guanidinopentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(p-trifluoromethylbenzyl)-4-(2-carboxyethyl)-7-(6-guanidinohexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(ethyl-5-valeroyl)-4-(2-carboxyethyl)-7-(5-guanidinopentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(ethyl-5-valeroyl)-4-(2-carboxyethyl)-7-(6-guanidinohexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(p-methoxybenzyl)-4-(2-carboxyethyl)-7-(5-guanidinopentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(p-methoxybenzyl)-4-(2-carboxyethyl)-7-(6-guanidinohexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(p-methylmethylbenzoyl)-4-(2-carboxyethyl)-7-(5-guanidinopentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(p-methylmethylbenzoyl)-4-(2-carboxyethyl)-7-(6-guanidinohexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(diphenylmethyl)-4-(2-carboxyethyl)-7-(6-guanidino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(diphenylmethyl)-4-(2-carboxyethyl)-7-(4-guanidino-1-butynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(1-napthyl)methyl-4-(2-carboxyethyl)-7-(5-guanidino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(1-napthyl)methyl-4-(2-carboxyethyl)-7-(6-guanidino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-(2-carboxyethyl)-7-(5-guanidino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-(2-carboxyethyl)-7-(6-guanidino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(p-phenoxybenzyl)-4-(2-carboxyethyl)-7-(5-guanidino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(p-phenoxybenzyl)-4-(2-carboxyethyl)-7-(6-guanidino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(m-phenoxybenzyl)-4-(2-carboxyethyl)-7-(5-guanidino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(m-phenoxybenzyl)-4-(2-carboxyethyl)-7-(6-guanidino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(p-trifluoromethylbenzyl)-4-(2-carboxyethyl)-7-(5-guanidino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(p-trifluoromethylbenzyl)-4-(2-carboxyethyl)-7-(6-guanidino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(ethyl-5-valeroyl)-4-(2-carboxyethyl)-7-(5-guanidino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(ethyl-5-valeroyl)-4-(2-carboxyethyl)-7-(6-guanidino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(p-methoxybenzyl)-4-(2-carboxyethyl)-7-(5-guanidino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(p-methoxybenzyl)-4-(2-carboxyethyl)-7-(6-guanidino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(p-methylmethylbenzoyl)-4-(2-carboxyethyl)-7-(5-guanidino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(p-methylmethylbenzoyl)-4-(2-carboxyethyl)-7-(6-guanidino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-(3(S)-butanoate)-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-(3(S)-butanoate)-7-(6-guanidino-1-hexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-(3(R)-butanoate)-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-(3(R)-butanoate)-7-(6-guanidino-1-hexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-((+/-)3-butanoate)-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-((+/-)3-butanoate)-7-(6-guanidino-1-hexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-(3(S)-phenyl-3-proprionate)-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-(3(S)-phenyl-3-proprionate)-7-(6-guanidino-1-hexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-(3(R)-phenyl-3-proprionate)-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-(3(R)-phenyl-3-proprionate)-7-(6-guanidino-1-hexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-((+/-)3-phenyl-3-proprionate)-7-(5-guanidino-1-pentyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-((+/-)3-phenyl-3-proprionate)-7-(6-guanidino-1-hexyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-(3(S)-butanoate)-7-(5-guanidino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-(3(S)-butanoate)-7-(6-guanidino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-(3(R)-butanoate)-7-(5-guanidino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-(3(R)-butanoate)-7-(6-guanidino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-((+/-)3-butanoate)-7-(5-guanidino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-((+/-)3-butanoate)-7-(6-guanidino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-(3(S)-phenyl-3-proprionate)-7-(5-guanidino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-(3(S)-phenyl-3-proprionate)-7-(6-guanidino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-(3(R)-phenyl-3-proprionate)-7-(5-guanidino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-(3(R)-phenyl-3-proprionate)-7-(6-guanidino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-((+/-)3-phenyl3-proprionate)-7-(5-guanidino-1-pentynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate,

1-(2-napthyl)methyl-4-((+/-)3-phenyl-3-proprionate)-7-(6-guanidino-1-hexynl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dionetrifluoroacetate.

EXAMPLE 16 ##STR50##1-methyl-4-(2-carboxyethyl)-8-(3-amino-1-propynyl)-3,4-dihydro1H-1,4-napthodiazepine-2,4-dione trifluoracetate

a) [4,5]-Benzoisatoic anhydride was prepared according to the methoddescribed in part (a) of example 1. Thus, 35 g of 3-amino-2-naphthoicacid (187 mMol) was dissolved in 500 mL of water containing 20 g ofpotassium carbonate. A solution of phosgene in toluene (1.93M, 290 mL)was added slowly with vigorous stirring. A precipitate appeared alongwith evolution of gas. Stirring was continued for 30 min after completeaddition of the phosgene. The precipitate was collected by suctionfiltration. The solid material was washed thoroughly with water andhexane and air dried yielding 37.7 g (95%) of [4,5]-benzoisatoicanhydride. M.p.>400° C. ¹ H NMR (CDCL₃): 12.0, s, 1H; 8.95, s, 1H; 8.3,d, J=7 Hz, 1H; 8.15, d, J=7 Hz, 1H; 7.85, t, J=7 Hz, 1H; 7.7, t, J= 7Hz, 1H; 7,7, s, 1H.

b) 10.3 g (48.3 mMol) of [4,5]-benzoisatoic anhydride was dissolved in50 mL of anhydrous N,N-dimethylformamide (DMF) and added dropwise to anice-cooled suspension of sodium hydride (97%, 1.25 g) in 50 mL of DMFwith gas evolution. After stirring an additional 30 min, 3.16 mL (105mol %) of methyl iodide was added to the solution. After one hour, thereaction mixture was poured over ice and the precipitated product wascollected by suction filtration and air dried, yielding 9.3 g (85%) ofN-methyl-[4,5]-benzoisatoic anhydride, a tan solid. M.p. 219°-222° C. ¹H NMR (d⁶ -DMSO): 8.8, s, 1H; 8.15, d, J=7 Hz, 1H; 8.0, d, J=7 Hz, 1H;7.85, s, 1H; 7.7, t, J=7 Hz, 1H; 7.55, t, J=7 Hz, 1H; 3.35, s, 3H.

Using the above procedure, but substituting the appropriate alkyl halidefor methyl iodide there may be prepared, for example, the followingcompounds:

N-benzyl-[4,5]-benzoisatoic anhydride,N-(2,4-diflurobenzyl)-[4,5]-benzoisatoic anhydride,N-(b-napthyl)methyl-[4,5]-benzoisatoic anhydride.

c) A solution of 20.0 g (89 mMol) of N-methyl-[4,5]-benzoisatoicanhydride, 20.5 g (133.5 mMol) of the hydrochloride salt of ethyl3-aminopropionate, and 18.6 mL (133.5 mMol) of triethylamine in 100 mLof DMF was stirred at 800° C. for four hr. The reaction mixture was thenpoured over ice containing citric acid and the precipitated product wascollected by suction filtration. The crude product was recrystallizedfrom benzene/hexane, yielding 24 g (60%) of3-(N-methylamino)-2-[N-(2-carboxyethyl)]-naphthocarboxamide ethyl ester,a yellow crystalline solid. MS (FAB) 300.1. ¹ H NMR (CDCL₃): 7.8, s, 1H;7.65, d, J=7 Hz, 1H; 7.6, d, J=7Hz, 1H; 7.4, t, J=7 Hz, 1H; 7.2, t, J=7Hz, 1H; 6.9, br s, 1H; 6.8, s, 1H; 4.2, q, J=7 Hz, 2H; 3.75, q, J=5 Hz,2H; 2.95, s, 3H; 2.65, t, J=5 Hz, 2H; 1.3, t, J=7 Hz, 3H.

Using the above procedure, but substituting the appropriate3-aminopropionate for ethyl 3-aminopropionate there may be prepared, forexample, the following compounds:

(±)-3-(N-methyl)amino-2-[N-(3-butanoate)]-naphthocarboxamide ethylester,

(±)-3-(N-methyl)amino-2-[N-(3-phenyl-3-phenyl-3-proprionate)]-naphthocarboxamideethyl ester,

(±)-3-(N-benzyl)amino-2-[N-(3-butanoate)]-naphthocarboxamide ethylester,

(±)-3-(N-benzyl)amino-2-[N-(3-phenyl-3-proprionate)]-naphthocarboxamideethyl ester,

(±)-3-(N-2,4-diflurobenzyl)amino-2-[N-(3-butanoate)]-naphthocarboxamideethyl ester,

(±)-3-(N-2,4-diflurobenzyl)amino-2-[N-(3-phenyl-3-proprionate)]-naphthocarboxamideethyl ester,

(±)-3-(N-(b-napthyl)methyl)amino-2-[N-(3-butanoate)]-naphthocarboxamideethyl ester,

(±)-3-(N-(b-napthyl)methyl)amino-2-[N-(3-phenyl-3-proprionate)]-naphthocarboxamideethyl ester.

d) To an ice-cooled solution of 5.0 g (17.5 mMol) of3-(N-methyl)amino-2-[N-(2-carboxyethyl)]-naphthocarboxamide ethyl esterand 2.68 mL (19 mMol) of triethylamine in 50 mL of methylene chloridewas added dropwise a solution of 1.59 mL 19(mMol) of bromoacetylbromide. After warming to room temperature, the solution was washed withaqueous citric acid and aqueous sodium bicarbonate solution, dried oversodium sulfate and evaporated. This material was dissolved in DMF (20mL) and added dropwise to a suspension of 97% sodium hydride (462 mg, 19mMol) at -15° C. After warming to room temperature the solution waspoured over ice/citric acid and extracted into ether. 3.1 g (52%) of1-methyl-4-(carboxyethyl)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dioneethyl ester, a yellow oil, was obtained after column chromatography onsilica gel. MS (FAB) 341. ¹ H NMR (CDCL₃): 8.4, s, 1H; 7.9, d, J=8.5, 1H; 7.8, d, J=8.5, 1H; 7.6, s, 1H; 7.45-7.6, m, 2H; 4.15, q, J=7 Hz, 2H;4.1, d, J=14 Hz, 3.95, t, J=7 Hz, 2H; 3.85, d, J=14 Hz, 1H; 3.5, s, 3H;2.75, m, 2H; 1.25,t, J=7 Hz, 3H.

Using the above procedure, but substituting the appropriatenaphthocarboxamide for3-(N-methyl)amino-2-[N-(2-carboxyethyl)]-naphthocarboxamide ethyl esterthere may be prepared, for example, the following compounds:

1-benzyl-4-(carboxyethyl)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dioneethyl ester

1-(2,4-diflurobenzyl)-4-(carboxyethyl)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dioneethyl ester

1-(b-napthyl)methyl-4-(carboxyethyl)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dioneethyl ester

(±)-1-methyl-4-(3-butanoate)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dioneethyl ester,

(±)-1-methyl-4-(3-phenyl-3-proprionate)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dioneethyl ester,

(±)-1-benzyl-2-(3-butanoate)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dioneethyl ester,

(±)-1-benzyl-2-(3-phenyl-3-proprionate)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dioneethyl ester,

(±)-1-(2,4-diflurobenzyl)-2-(3-butanoate)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dioneethyl ester,

(±)-1-(2,4-diflurobenzyl)-2-(3-phenyl-3-proprionate)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dioneethyl ester,

(±)-1-(b-napthyl)methyl-2-(3-butanoate)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dioneethyl ester,

(±)-1-(b-napthyl)methyl-4-(3-phenyl-3-proprionate)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dioneethyl ester.

e)1-Methyl-4-(ethoxycarbonylethyl)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dione(3.1 g, 9.1 mMol) was placed in an ice bath and 4 mL of fuming nitricacid was added. After stirring for 1 hr at 0° C. the reaction wasallowed to warm to room temperature and stirred for an additional 2 hr.The reaction mixture was poured into ice water and extracted with ethylacetate, dried (sodium sulfate) and evaporated to yield a yellow solid.Thin layer chromatography (TLC) and ¹ H NMR analysis indicated a mixtureof nitrated products. The crude mixture was purified by columnchromatography (SiO₂) to yield 600 mgs (17%) of8-Nitro-1-methyl-4-(ethoxycarbonylethyl)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dione.¹ H NMR (CDCl₃, dTMS) 8.8 (1H, d, ⁴ J_(HH) =2 Hz), 8.6 (1H, s), 8.3 (1H,dd, ² J_(HH) =9 Hz, ⁴ J_(HH) =2 Hz, 7.95 (1H, d, ³ J_(HH) =9 Hz), 7.7(1H, s), 4.15 (2H, q, ³ J_(HH) =8 Hz), 4.1 (1H, d, ² J_(HH) =14 Hz), 4.0(2H, t, ³ J_(HH) =7 Hz), 3.95 (1H, ² J_(HH) =14 Hz), 3.5 (3H, s), 2.75(2H, m), 1.25 (3H, t, ³ J_(HH) =8 Hz).

Using the above procedure, but substituting the appropriatenaphthocarboxamide for3-(N-methyl)amino-2-[N-(2-carboxyethyl)]naphthocarboxamide ethyl esterthere may be prepared, for example, the following compounds:

1-(2,4-diflurobenzyl)-4-(carboxyethyl)-8-nitro-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dioneethyl ester,

(±)-1-methyl-4-(3-butanoate)-8-nitro-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dioneethyl ester,

(±)-1-(2,4-diflurobenzyl)-2-(3-butanoate)-8-nitro-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dioneethyl ester.

f)1-Methyl-4-(carboxylethyl)-8-nitro-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dioneethyl ester (600 mg, 1.56 mMol) was hydrogenated in ethanol with 200 mgof 10% palladium on carbon catalyst at 50 psi hydrogen for 24 hr afterwhich time tlc indicated that reduction was complete. The catalyst wasremoved by filtration through Celite®, and the filtrate was evaporatedyielding ca. 500 mg of1-methyl-4-(carboxylethyl)-8-amino-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dioneethyl ester. ¹ H NMR (CDCL₃): 8.1, s, 1H; 7.6, d, J=9.5 Hz, 1H; 7.45, s,1H; 7.15, s, 1H; 7.1, d, J=9.5 Hz, 1H; 4.15, q, J=8 Hz, 2H; 4.1, d, J=14Hz, 1H; 3.95, t, J=7 Hz, 2H; 3.8, d, J=14 Hz, 1H; 3.4, s, 3H; 2.7, m,2H; 1.2, t, J=8 Hz. This material was dissolved in 4 mL of watercontaining 117 mL of concentrated sulfuric acid and cooled to 0° C. withan ice bath. Sodium nitrite (97 mg, 1.5 mMol) in 2 mL of water was addedto the solution dropwise, and the temperature of the solution wasallowed to rise to room temperature over one hour. 2.6 g (14 mMol) ofpotassium iodide was added to the solution and stirring was continuedfor 24 hr. The reaction mixture was diluted with water and extractedwith ethyl acetate, and the ethyl acetate was dried (sodium sulfate) andevaporated. Chromatography on silica gel yielded ca. 240 mg of8-Iodo-1-methyl-4-(ethoxycarbonylethyl)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dioneas an amber oil. MS (FAB) 466.9. ¹ H NMR (CDCL₃): 8.3, s, 2H; 7.8, dd,J= 8.5 Hz, J'=1.5 Hz, 1H; 7.55, s, 1H; 7.55, d, J=8.5 Hz, 1H; 4.15, q,J=7 Hz, 2H; 4.1, d, J=14 Hz, 1H; 3.95, t, J=7 Hz, 2H; 3.9, d, J=14 Hz,1H; 3.5s, 3H; 2.75, m, 2H; 1.25, t, J=7 Hz.

Using the above procedure, but substituting the appropriate8-nitro-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dione for1-methyl-4-(2-carboxylethyl)-8-nitro-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dioneethyl ester there may be prepared, for example, the following compounds:

1-(2,4-diflurobenzyl)-4-(carboxyethyl)-8-iodo-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dioneethyl ester,

(±)-1-methyl-4-(3-butanoate)-8-iodo-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dioneethyl ester,

(±)-1-(2,4-diflurobenzyl)-2-(3-butanoate)-8-iodo-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dioneethyl ester.

g)1-Methyl-4-(ethoxycarbonylethyl)-8-Iodo-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dione(100 mg, 215 mM) was combined in 1 mL of ethyl acetate with 166 mg (500m %) of N-t-butoxycarbonylpropargyl amine, 15 mg (10 mol %) ofbistriphenylphosphine palladium dichloride, and 299 mL (10 X excess) oftriethylamine. The apparatus was degassed and an atmosphere of nitrogenwas introduced. 8.2 mg (20 mol %) of cuprous iodide was added and thesolution was again degassed and nitrogen atmosphere was replaced. After24 hr the reaction mixture was diluted with ethyl acetate and washedsuccessively with aqueous citric acid and aqueous sodium bicarbonate,dried (sodium sulfate) and evaporated. The residue was chromatographedon silica gel, yielding 110 mg of1-methyl-4-(carboxylethyl)-8-(3-t-butyloxycarbonylamino-1-propynyl)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dione.MS (FAB) 494.1. ¹ H NMR (CDCL₃): 8.35, s, 1H; 7.95, s, 1H; 7.75, d,J=8.5 Hz, 1H; 7.55, s, 1H; 7.5, d, J=8.5 Hz, 1H; 4.9, br s, 1H; 4.2, brs, 2H; 4.2, q, J=7 Hz, 2H; 4.1, d, J=14 Hz, 1H; 4.0, t, J=7 Hz, 2H; 3.9,d, J=7 Hz, 1H; 3.5, s, 3H; 2.75, m, 2H; 1.5, s, 9H; 1.25, t, J=7 Hz, 3H.

Using the above procedure, but substituting the appropriate8-iodo-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dione for1-methyl-4-(2-carboxylethyl)-8-iodo-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dioneethyl ester there may be prepared, for example, the following compounds:

1-(2,4-diflurobenzyl)-4-(carboxyethyl)-8-(3-t-butyloxycarbonylamino-1-propynyl)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dioneethyl ester,

(±)-1-methyl-4-(3-butanoate)-8-(3-t-butyloxycarbonylamino-1-propynyl)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dioneethyl ester,

(±)-1-(2,4-diflurobenzyl)-2-(3-butanoate)-8-(3-t-butyloxycarbonylamino-1-propynyl)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dioneethyl ester,

1-(2,4-diflurobenzyl)-4-(carboxyethyl)-8-(4-t-butyloxycarbonylamino-1-butynyl)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dioneethyl ester,

(±)-1-methyl-4-(3-butanoate)-8-(4-t-butyloxycarbonylamino-1-butynyl)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dioneethyl ester,

(±)-1-(2,4-diflurobenzyl)-2-(3-butanoate)-8-(4-t-butyloxycarbonylamino-1-butynyl)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dioneethyl ester.

h) To a stirred solution of1-methyl-4-(carboxyethyl)-8-(3-t-butyloxycarbonylamino-1-propynyl)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dioneethyl ester (110 mg, 0.22 mMol) in 8 mL of methanol was added 1 mL of 1Nsodium hydroxide solution. After 4 hr no more starting material wasdetected by tlc. The solvent was removed in vacuo and the residue wastreated with 10 mL of 4N HCl in dioxane. After 2 hr the solvent wasremoved in vacuo and the residue was purified by reverse phase HPLC,yielding 25 mg of1-methyl-4-(carboxyethyl)-8-(3-amino-1-propynyl)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dione.HRMS (FAB) molecular ion m/z=366.1454 (cald. C₂₀ H₂₀ N₃ O₄, 366.4004). ¹H NMR (CD₃ OD): 7.9, s, 1H; 7.7, s, 1H; 7.55, d, J=8 Hz, 1H; 7.45, s,1H; 7.2, d, J=8 Hz, 1H; 3.75, d, J=14 Hz, 1H; 3.65, s, 2H; 3.55, d, J=14Hz, 1H; 3.5, m, 2H; 3.05, s, 3H; 2.2, q, J=7 Hz, 2H.

Using the above procedure, but substituting the appropriate8-(t-butyloxycarbonylamino-1-alkynyl)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dionefor1-methyl-4-(carboxyethyl)-8-(3-t-butyloxycarbonylamino-1-propynyl)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dioneethyl ester there may be prepared, for example, the following compounds:

1-(2,4-diflurobenzyl)-4-(carboxyethyl)-8-(3-amino-1-propynyl)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dione,

(±)-1-methyl-4-(3-butanoate)-8-(3-amino-1-propynyl)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dione,

(±)-1-(2,4-diflurobenzyl)-4-(3-butanoate)-8-(3-amino-1-propynyl)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dione,

1-(2,4-diflurobenzyl)-4-(carboxyethyl)-8-(4-amino-1-butynyl)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dione,

(±)-1-methyl-4-(3-butanoate)-8-(4-amino-1-butynyl)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dione,

(±)-1-(2,4-diflurobenzyl)-4-(3-butanoate)-8-(4-amino-1-butynyl)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dione.

EXAMPLE 17 ##STR51##1-Methyl-4-(carboxyethyl)-8-(3-guanidino-1-propynyl)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dione

The title compound was prepared from1-methyl-4-(carboxyethyl)-8-(3-amino-1-propynyl)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dione(50 mg) according to the procedure described in Example 2. HRMS (FAB)molecular ion m/z=408.1672 (cald. C₂₁ H₂₂ N₅ O₄, 408.1672). ¹ H NMR (CD₃OD): 7.9, s, 1H; 7.7, s, 1H; 7.55, d, J=8 Hz, 1H; 7.45, s, 1H; 7.2, d,J=8 Hz, 1H; 3.75, d, J=14 Hz, 1H; 3.65, s, 2H; 3.55, d, J=14 Hz, 1H;3.5, m, 2H; 3.05, s, 3H; 2.2, q, J=7 Hz, 2H.

Using the above procedure, but substituting the appropriate8-(amino-1-alkynyl)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dione for1-methyl-4-(carboxyethyl)-8-(3-amino-1-propynyl)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dionethere may be prepared, for example, the following compounds:

1-(2,4-diflurobenzyl)-4-(carboxyethyl)-8-(3-guanidino-1-propynyl)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dione,

(±)-1-methyl-4-(3-butanoate)-8-(3-guanidino-1-propynyl)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dione,

(±)-1-(2,4-diflurobenzyl)-2-(3-butanoate)-8-(3-guanidino-1-propynyl)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dione,

1-(2,4-diflurobenzyl)-4-(carboxyethyl)-8-(4-guanidino-1-butynyl)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dione,

(±)-1-methyl-4-(3-butanoate)-8-(4-guanidino-1-butynyl)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dione,

(±)-1-(2,4-diflurobenzyl)-2-(3-butanoate)-8-(4-guanidino-1-butynyl)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dione.

EXAMPLE 18 ##STR52##1-Methyl-4-(carboxyethyl)-8-(3-amino-1-propyl)-3,4,7,8,9,10-hexahydrohydro-1H-1,4-naphthodiazepine-2,5-dione

1-Methyl-4-(carboxyethyl)-8-(3-amino-1-propynyl)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dione(50 mg) was reduced with 10 mg of 10% Pd/C in 10 mL of 5:1 water ethanolat 45 psi of hydrogen in a Parr hydrogenation apparatus for 24 hryielding, after filtration through Celite® and purification by reversephase HPLC, the title compound. MS (FAB) 374.1 . ¹ H NMR (CD₃ OD): 7.4,s, 1H; 7.0, s, 1H; 3.95, d, J=14 Hz, 1H; 3.8, d, J=14 Hz, 1H; 3.6, m,2H; 3.2, s, 3H; 2.85, t, J=7 Hz, 2H; 2.4, t, J=7 Hz, 2H; 1.9, m, 1H;1.65, m, 4H; 1.4, m, 4H.

Using the above procedure, but substituting the appropriate8-(amino-1-alkynyl)-3,4-dihydro-1H-1,4-naphthodiazepine-2,5-dione for1-methyl-4-(carboxyethyl)-8-(3-amino-1-propynyl)-3,4,7,8,9,10-hexahydrohydro-1H-1,4-naphthodiazepine-2,5-dionethere may be prepared, for example, the following compounds:

1-(2,4-diflurobenzyl)-4-(carboxyethyl)-8-(3-guanidino-1-propynyl)-3,4,7,8,9,10-hexahydrohydro-1H-1,4-naphthodiazepine-2,5-dione,

(±)-1-methyl-4-(3-butanoate)-8-(3-guanidino-1-propynyl)-3,4,7,8,9,10-hexahydrohydro-1H-1,4-naphthodiazepine-2,5-dione,

(±)-1-(2,4-diflurobenzyl)-2-(3-butanoate)-8-(3-guanidino-1-propynyl)-3,4,7,8,9,10-hexahydrohydro-1H-1,4-naphthodiazepine-2,5-dione,

EXAMPLE 19 ##STR53##2-(2-carboxyethyl)-8-(4-amidinobenzyloxy)-2,3,4,5-tetrahydro-1H-2-benzazepin-1-onetrifluoroacetate

a) A solution of 7-methoxytetralone (Fluka Chemical, 100.0 g, 0.567 mol)in dry pyridine (600 mL) was treated with hydroxylamine hydrochloride(Fluka, 43.0 g, 0.618 mol) and the resulting dark yellow solution wasstirred at room temperature for 1 hour. The solution was thenconcentrated in vacuo, and azeotroped with several volumes of toluene,then partitioned between ethyl acetate and brine. The combined organiclayers were dried (K₂ CO₃), filtered, and concentrated in vacuo. Theresidue was crystallized from ethyl acetate/hexanes to yield 88 g (81%)of the oxime as a waxy solid.

b) Following a procedure of Tomita, et. al., J. Chem. Soc. C 1969, 183,7-methoxytetralone oxime (45.0 g, 0.235 mol) was mixed with solidtrichloroacetic acid (150 g), and the resulting suspension heated to ca.80 C., at which time a violent exotherm ensued, yielding a black solidmixture. The residue was cooled, partitioned between ethyl acetate andsaturated aqueous sodium bicarbonate solution, and the combined organiclayers were concentrated in vacuo. The residue was purified bychromatography over silica gel to yield 10.0 g (22%) of8-methoxy-2,3,4,5-tetrahydro-1H-2-benzazepin-1-one. An analytical samplewas obtained by recrystallization from CH₂ Cl₂ /hexanes to yieldcolorless crystals: mp. 99°-101° C. (lit. (see above) 100°-101° C.); ¹ HNMR(CDCl₃) d7.35(brs, 1H), 7.30(d, J=3 Hz, 1H), 7.10(d, J=9 Hz, 1H),6.95(dd, J=3, 9 Hz, 1H), 3.82(s, 3H), 3.10(q, J=6 Hz, 2H), 2.80(t, J=6Hz, 2H), 1.98(m, 2H).

c) A solution of 8-methoxy-2,3,4,5-tetrahydro-1H-2-benzazepin-1-one(10.0 g 0.052 mol) in N,N-dimethylformamide (30 mL) and allylbromide (23mL, 0.260 mL) was treated with NaH (60% by wt. dispersion in oil, 2.50g, 0.063 mol) and the resulting grey suspension stirred at roomtemperature under an atmosphere of argon. Gas evolution was noted. After15 minutes, the solution was diluted with brine and partitioned betweenethyl acetate and brine. The combined organic layers were concentratedin vacuo and purified by chromatography over silica gel eluting with agradient of hexane to 1:1 ethyl acetate/hexane to yield 8 g (83%) of2-allyl-8-methoxy-2,3,4,5-tetrahydro-1H-2-benzazepin-1-one as acolorless oil: ¹ H NMR(CDCl₃) d7.23(m, 1H), 7.03(d, J=9 Hz, 1H),6.90(dd, J=3, 9 Hz, 1H), 5.91(m, 1H), 5.23(m, 2H), 4.20(d, J=6 Hz, 2H),3.82(s, 3H), 3.18(t, J=6 Hz, 2H), 2.72(t, J=6 Hz, 2H), 1.96(pentet, J=6Hz, 2H); ¹³ C NMR(CDCl₃) d170.59(CO), 158.42(NCO), 136.88, 133.81,129.43, 129.35, 129.33, 117.56, 117.54, 112.98, 55.26, 49.43, 45.37,29.57, 29.22; MS(FAB) m/z=232.1(MH⁺).

d) A solution of2-allyl-8-methoxy-2,3,4,5-tetrahydro-1H-2-benzazepin-1-one (8.0 g, 0.043mol) in dry tetrahydrofuran (40 mL) was treated with 9-borabicyclononane(1.0M in THF) and the resulting mixture was stirred for 18 hours at roomtemperature. The solution was then diluted with EtOH (50 mL), cooled to0° C. (ice bath), and treated with 15% aqueous NaOH (15 mL) followed by30% aqueous H₂ O₂ (10 mL). The resulting mixture was stirred for 1 hourat 0° C., then treated cautiously with saturated aqueous sodiumthiosulfate (50 mL). The mixture was partitioned between ethyl acetateand brine, and the combined organic layers were concentrated in vacuo,and the residue was purified by chromatography over silica gel elutingwith ethyl acetate to yield 6.5 g (60%) of2-(3-hydroxypropyl)-8-methoxy-2,3,4,5-tetrahydro-1H-2-benzazepin-1-oneas a colorless oil; ¹ H NMR(CDCl.sub. 3) d7.19(s, 1H), 7.06(d, J=9 Hz,1H, 6.92(dd, J=3, 9 Hz, 1H), 4.30(brs, 1H), 3.82(s, 3H), 3.71(t, J=6 Hz,2H), 3.61(brs, 2H), 3.18(t, J=6 Hz, 2H), 2.72(t, J=6 Hz, 2H),2.02(pentet, J=6 Hz, 2H), 1.79(pentet, J=6 Hz, 2H); ¹³ C NMR(CDCl₃)d172.25(CO), 158.51(NCO), 136.34, 129.53, 117.46, 112.94, 58.19, 55.42,46.16, 43.30, 30.91, 29.45, 29.12; MS (FAB) m/z=250.1(MH⁺); HRMS (FAB,MH⁺) m/z=249.1364 (cald C₁₄ H₁₉ NO₃ : 249.1364).

e) A solution of2-(3-hydroxypropyl)-8-methoxy-2,3,4,5-tetrahydro-1H-2-benzazepin-1-one(6.50 g, 0.026 mol) in CH₂ Cl₂ was added, at -78° C. (CO₂ /acetone), toa solution of (COCl)₂ (4.50 mL, 0.052 mol) and DMSO (7.4 mL, 0.104 mol)in CH₂ Cl₂ (100 mL) at -78° C. After stirring for 15 minutes at -78° C.,the mixture was treated with NEt₃ (30 mL, 0.208 mol), and the bathremoved. The CH₂ Cl₂ solution was washed with brine, dried (MgSO₄) andconcentrated in vacuo. The residue was immediately dissolved inN,N-dimethylformamide (30 mL) and MeOH (30 mL), and treated, inportions, with pyridinium dichromate (30 g total). After stirring for 24hours, the dark brown suspension was diluted with ethyl acetate andfiltered, and the filtrate was partitioned between ethyl acetate andbrine. The combined organic layers were washed with water, brine, dried(MgSO₄) and concentrated in vacuo. The residue was purified bychromatography over silica gel eluting with a gradient of 10% ethylacetate/hexane to 100% ethyl acetate to yield 2.5 g (35%) of2-(2-carboxyethyl)-8-methoxy-2,3,4,5-tetrahydro-1H-2-benzazepin-1-onemethyl ester as a colorless oil; ¹ H NMR(CDCl₃) d7.18(d, J=3 Hz, 1H),7.02(d, J=9 Hz, 1H), 6.88(dd, J=3, 9 Hz, 1H), 3.83(t, J=6 Hz, 2H),3.80(s, 3H), 3.69(s, 3H), 3.23(t, J=6 Hz, 2H), 2.78(t, J=6 Hz, 2H),2.67(t, J=6 Hz, 2H), 1.96(m, 2H); ¹³ C NMR(CDCl₃) d172.41(CO),171.15(CO), 158.50, 136.80, 129.58, 129.40, 117.34, 112.86, 55.42,51.78, 47.37, 44.13, 33.64, 29.85, 29.14; MS(FAB) m/z=278.1 (MH⁺);HRMS(FAB, MH⁺) m/z=278.1392 (cald for C₁₅ H₁₉ NO₄ : 277.1313).

f) A solution of2-(2-carboxyethyl)-8-methoxy-2,3,4,5-tetrahydro-1H-2-benzazepin-1-onemethyl ester (3.20 g, 0.011 mol) in CH₂ Cl₂ was added to a suspension ofAlCl₃ (4.70 g, 0.034 mol) and n-propanethiol (5.3 mL, 0.057 mol) at 0°C. (ice bath), and the resulting mixture stirred for 10 minutes at roomtemperature. The mixture was diluted with saturated aqueous sodiumbicarbonate (50 mL), and the resulting white suspension stirred for 1hour. The gelatinous mixture was filtered, and the filtrate was dried(MgSO₄) and concentrated in vacuo to yield 2.0 g (85%) of2-(2-carboxyethyl)-8-hydroxy-2,3,4,5-tetrahydro-1H-2-benzazepin-1-onemethyl ester as a colorless oil; ¹ H NMR(CD₃ OD) d7.08(d, J=9 Hz, 1H,7.02(d, J=3 Hz, 1H), 6.78(dd, J=3, 9 Hz, 1H), 3.05 (t, J=6 Hz, 2H),2.72(t, J=6 Hz, 2H), 1.97(t, J=6 Hz, 2H).

g) A suspension of2-(2-carboxyethyl)-8-hydroxy-2,3,4,5-tetrahydro-1H-2-benzazepin-1-onemethyl ester (250 mg, 0.950 mmol), p-cyanobenzylbromide (186 mg, 0.950mmol) and K₂ CO₃ (500 mg) in N,N-dimethylformamide (20 mL) was stirredvigorously at room temperature under an atmosphere of argon. After 1hour, the suspension was diluted with ethyl acetate (100 mL), washedwith water and brine, dried (Na₂ SO₄) and concentrated in vacuo. Theresidue was purified by chromatography over silica gel to yield 150 mg(40%) of2-(2-carboxyethyl)-8-(4-cyanobenzyloxy)-2,3,4,5-tetrahydro-1H-2-benzazepin-1-onemethyl ester as a colorless oil; ¹ H NMR(CDCl₃) d7.66(d, J=6 Hz, 1H),7.54(d, J=6 Hz, 1H), 7.00(dd, J=3, 9 Hz, 1H), 5.13(s, 2H), 3.84(t, J=6Hz, 2H), 3.70(s, 3H), 3.24(t, J=6 Hz, 2H), 2.72(m, 4H), 1.98(pentet, J=6Hz, 2H); ¹³ C NMR(CDCl₃) d172.27(CO), 170.82(CO), 157.05, 142.32,137.01, 132.39, 132.32, 130.45, 129.63, 127.52, 118.66, 117.83, 113.98,111.53, 68.90, 51.76, 47.31, 44.14, 33.58, 29.76, 29.13; MS(FAB)m/z=379.1(MH⁺).

h) A solution of2-(2-carboxyethyl)-8-(4-cyanobenzyloxy)-2,3,4,5-tetrahydro-1H-2-benzazepin-1-onemethyl ester (150 mg, 0.400 mmol) in 50 mL of 1:1 pyridine-NEt₃ wassaturated with H₂ S, and heated at 50° C. under argon. After 1 hour, thesolvents were removed in vacuo. The residue was dissolved in CH₂ Cl₂ (20mL) and treated with iodomethane (4 mL), and the resulting mixtureheated at reflux for 1 hour. The solvents were removed in vacuo, and theresidue was dissolved in MeOH and treated with an excess of NH₄ OAc (1g). The resulting suspension was stirred for 15 minutes at 60° C. TheMeOH was then removed, and the residue was treated with 50% NaOH (3 mL)in tetrahydrofuran (20 mL), and stirred for 15 minutes at roomtemperature. The mixture was then diluted with trifluoroacetic acid, andthe volatiles were removed in vacuo. The residue was purified by HPLC(1/2 C-18 reverse-phase column, eluting with a solvent gradient of 1:9acetonitrile(0.1% TFA)/water (0.1% TFA) time 0 to 10 minutes, to 1:1acetonitrile(0.1% TFA)/water (0.1% TFA) time 10 to 40 minutes, flow 10mL/min, R_(t) =30.5 min, mu detection 254 nM), to give 18.5 mg (9%) of2-(2-carboxyethyl)-8-(4-amidinobenzyloxy)-2,3,4,5-tetrahydro-1H-2-benzazepin-1-onetrifluoroacetate as a yellowish-brown solid after lyophylization; ¹ HNMR(CD₃ OD) d7.66(d, J=6 Hz, 1H), 7.54(d, J=6 Hz, 1H), 7.00(dd, J=3, 9Hz, 1H), 5.13(s, 2H), 3.84(t, J=6 Hz, 2H), 3.70(s, 3H), 3.24(t, J=6 Hz,2H), 2.72(m, 4H), 1.98(m, J=6 Hz, 2H); MS(FAB) m/z=381.1688 (MH⁺).

EXAMPLE 20 ##STR54##2-(2-carboxyethyl)-8-(8-aminooctyloxy)-2,3,4,5-tetrahydro-1H-2-benzazepin-1-onetrifluoroacetate

a) A solution of2-allyl-8-methoxy-2,3,4,5-tetrahydro-1H-2-benzazepin-1-one (1.10 g,0.0047 mol) in CH₂ Cl₂ (20 mL) was treated at 0° C. with BBr₃ (1M in CH₂Cl₂, 9.50 mL), and the resulting mixture stirred at 0° C. for 30minutes. The solution was poured over ice, NaHCO₃ was added, and thesolution was extracted with CH₂ Cl₂. The combined organic layers weredried (MgSO₄), filtered, and concentrated in vacuo to yield ca. 1.0 g(100%) of 2-allyl-8-hydroxy-2,3,4,5-tetrahydro-1H-2-benzazepin-1-one asa colorless oil; ¹ H NMR(CDCl₃) d8.2(brs, 1H), 7.47(s, 1H), 6.95(d, J=6Hz, 1H), 6.84(dd, J=3, 6 Hz, 1H), 5.89(m, 1H), 5.22(m, complex, 2H),4.20(d, J= 6 Hz, 2H), 3.18(t, J=6 Hz, 2H), 2.66(t, J=6 Hz, 2H), 2.15(s,1H), 1.96(m, 2H); ¹³ C NMR(CDCl₃) d171.65(CO), 156.01, 135.68, 133.27,129.55, 128.46, 118.51, 118.05, 115.91, 53.46, 49.81, 45.83, 30.87,29.76, 29.12.

b) A suspension of2-allyl-8-hydroxy-2,3,4,5-tetrahydro-1H-2-benzazepin-1-one (1.0 g,0.0049 mol), 8-azido-1-(toluenesulfonyloxy)octane (1.50 g, 0.0049 mol)and K₂ CO₃ in N,N-dimethylformamide (20 mL) was stirred vigorously underargon, and heated at 65° C. for 18 hours. The solution was thenpartitioned between ethyl acetate and brine, and the combined organiclayers were washed with water, dried (K₂ CO₃), filtered, andconcentrated in vacuo. The residue was purified by chromatography oversilica gel to yield 920 mg (51%) of2-allyl-8-(8-azidooctyloxy)-2,3,4,5-tetrahydro-1H-2-benzazepin-1-one asa colorless oil; ¹ H NMR(CDCl₃) d7.47(s, 1H), 6.95(d, J=6 Hz, 1H),6.84(dd, J=3, 6 Hz, 1H), 5.89(m, 1H), 5.22(m, complex, 2H), 4.20(d, J=6Hz, 2H), 3.95 (t, J=6 Hz, 2H), 3.22(t, J=6 Hz, 2H), 3.18(t, J=6 Hz, 2H),2.66(t, J=6 Hz, 2H), 1.90(t, J=6 Hz, 2H), 1.79(t, J=6 Hz, 2H), 1.60(m,4H), 1.35(m, 6H).

c) A solution of2-allyl-8-(8-azidooctyloxy)-2,3,4,5-tetrahydro-1H-2-benzazepin-1-one(920 mg, 2.48 mmol) in tetrahydrofuran (20 mL) was treated with9-borabicyclononane (0.5M/THF, 10 mL, 5.00 mmol), and the mixture wasstirred under argon at room temperature for 18 hours. The mixture wasthen cooled in an ice bath, and EtOH (5 mL) followed by 15% aqueous NaOH(10 mL) and 30% H₂ O₂ (15 mL) were added. The mixture was stirred for 1hour, then saturated aqueous sodium thiosulfate was added (20 mL). Thesolution was partitioned between ethyl acetate and brine, and thecombined ethyl acetate layers were dried (MgSO₄), filtered, andconcentrated in vacuo. The residue was purified by chromatography oversilica gel to yield 400 mg (42%) of2-(3-hydroxypropyl)-8-(8-azidooctyloxy)-2,3,4,5-tetrahydro-1H-2-benzazepin-1-oneas a colorless oil; ¹ H NMR(CDCl₃) d7.20(d, J=3 Hz, 1H), 7.04(d, J=6 Hz,1H), 6.91(dd, J=3, 6 Hz, 1H), 3.96(t, J=6 Hz, 2H), 3.72(t, J=6 Hz, 2H),3.61(t, J=6 Hz, 2H), 3.26(t, J=6 Hz, 2H), 3.18(t, J=6 Hz, 2H), 2.73(t,J=6 Hz, 2H), 2.02(t, J=6 Hz, 2H), 1.77(m, 4H), 1.60(m, 2H), 1.36(m, 8H).

d)2-(3-hydroxypropyl)-8-(8-azidooctyloxy)-2,3,4,5-tetrahydro-1H-2-benzazepin-1-onewas subjected to standard Swern conditions followed by PDC oxidation asdescribed in part (e) of Example 14 to yield 140 mg (45%) of2-(2-carboxyethyl)-8-(8-azidooctyloxy)-2,3,4,5-tetrahydro-1H-2-benzazepin-1-onemethyl ester as a colorless oil; ¹ H NMR(CDCl₃) d7.18(d, J=3 Hz, 1H),7.00(d, J=9 Hz, 1H), 6.89(dd, J=3, 9 Hz, 1H), 3.96(t, J=6 Hz, 2H),3.84(t, J=6 Hz, 2H), 3.70(s, 3H), 3.26(m, 4H), 2.74(m, 4H), 1.97(t, J=6Hz, 2H), 1.77(t, J=6 Hz, 2H), 1.60(t, J=6 Hz, 2H), 1.35(m, 6H); ¹³ CNMR(CDCl₃) d 172.38(CO), 171.21(CO), 158.04, 136.72, 129.40, 129.34,117.78, 113.57, 68.05, 51.76, 51.41, 47.37, 44.13, 33.64, 29.86, 29.13,19.02, 28.77, 26.59, 25.87; MS(FAB) 417.2(MH⁺).

e) A solution of2-(2-carboxyethyl)-8-(8-azidooctyloxy)-2,3,4,5-tetrahydro-1H-2-benzazepin-1-onemethyl ester (70 mg, 0.168 mmol) in MeOH (1 mL) was treated with 10%Pd/C (20 mg) and the resulting suspension was reduced under anatmosphere of hydrogen (30 psi) for 2 hours. The solution was thenfiltered through Celite®, and the filtrate was concentrated in vacuo.The residue was dissolved in tetrahydrofuran (1 mL) and treated with 50%NaOH (0.5 mL), and the resulting mixture was stirred at roomtemperature. After 1 hour, the solution was treated with trifluoroaceticacid (1 mL), and concentrated in vacuo. The white paste remaining waspurified by HPLC (1/2' C-18 reverse-phase column) eluting with agradient of 3:7 methanol (0.1% trifluoroaceate)/water (0.1%trifluoroaceate), time 0 to 10 min, to 7:3 methanol(0.1%trifluoroaceate)/water(0.1% trifluoroaceate), time 10 to 40 min, toyield 30 mg (36%) of2-(2-carboxyethyl)-8-(8-aminooctyloxy)-2,3,4,5-tetrahydro-1H-2-benzazepin-1-oneas a colorless oil; ¹ H NMR(CD₃ OD) d7.095(m, 2H), 6.96(dd, J=3, 9 Hz,1H), 3.98(t, J=6 Hz, 2H), 3.83(t, J=6 Hz, 2H), 3.27(m, 4H), 2.90(t, J= 6Hz, 2H), 2.69(m, 4H), 2.03(t, J=6 Hz, 2H), 1.78(t, J=6 Hz, 2H), 1.64(t,J=6 Hz, 2H), 1.40(m, 6H); MS(FAB) m/z=377.1(MH⁺ -TFA).

EXAMPLE 21 ##STR55##2-(2-carboxyethyl)-8-(8-guanadinooctyloxy)-2,3,4,5-tetrahydro-1H-2-benzazepin-1-onetrifluoroacetate

a) A solution of2-(2-carboxyethyl)-8-(8-aminooctyloxy)-2,3,4,5-tetrahydro-1H-2-benzazepin-1-onetrifluoroacetate (30 mg, 0.061 mmol) in saturated aqueous KHCO₃ (2 mL)was treated with formamidine sulfonic acid (85 mg, 1.08 mmol) and theresulting mixture was stirred at room temperature for 20 minutes. Themixture was neutralized with acetic acid, and the residue was purifiedby HPLC (1/2' C-18 reverse-phase column) eluting with a gradient of 3:7methanol (0.1% trifluoroaceate)/water (0.1% trifluoroaceate), time 0 to10 min, to 7:3 methanol(0.1% trifluoroaceate)/water(0.1%trifluoroaceate), time 10 to 40 min, to yield 7.3 mg (25%) of2-(2-carboxyethyl)-8-(8-guanadinooctyloxy)-2,3,4,5-tetrahydro-1H-2-benzazepin-1-onetrifluoroacetate as a light brown solid; ¹ H NMR(CD₃ OD) d7.09(m, 2H),6.96(dd, J=3, 9 Hz, 1H), 3.98(t, J= 6 Hz, 2H), 3.83(t, J=6 Hz, 2H),3.33(m, 4H), 2.91(t, J=6 Hz, 2H), 2.69(t, J=6 Hz, 4H), 2.30(m, 2H),1.75(m, 2H), 1.65(m, 2H), 1.40(m, 6H); ¹³ C NMR(CD₃ OD) d175.9(CO),160.0, 137.0, 131.16, 130.79, 118.66, 114.81, 69.17, 45.33, 40.78,34.32, 31.15, 30.27, 30.18, 30.15, 30.04, 28.59, 27.39, 27.06; MS(FAB)m/z=419.2(MH⁺).

EXAMPLE 22 ##STR56##2-(2-carboxyethyl)-8-(5-aminopentynyl)-2,3,4,5-tetrahydro-1H-2-benzazepin-1-onetrifluoroacetate

a) A solution of2-(2-carboxyethyl)-8-hydroxy-2,3,4,5-tetrahydro-1H-2-benzazepin-1-onemethyl ester (2.20 g, 0.00836 mol) and NEt₃ (1.40 mL, 0.0100 mol) in CH₂Cl₂ (20 mL) was cooled to 0° C. (ice bath) and treated withtrifluoromethanesulfonic anhydride (1.70 mL, 0.0100 mol), and theresulting mixture stirred to 30 minutes. The mixture was thenpartitioned between ethyl acetate and saturated aqueous NaHCO₃. Thecombined organic layers were dried (MgSO₄), filtered, and concentratedin vacuo to an oil, used immediately without purification. A solution ofthe triflate (400 mg, 1.00 mmol) and5-((tert-butyloxy)carbonyl)amino-2-pentyne (366 mg, 2.00 mmol) in NEt₃(10 mL) was treated with bis-triphenylphosphine palladium dichloride (20mg) and CuI (10 mg), and the resulting mixture was de-gassed thoroughlywith argon, and heated at reflux for 12 hours. The solution was thencooled, and volatiles removed in vacuo, and the residue was purified bychromatography over silica gel eluting with 1:1 ethyl acetate/hexanes toyield 400 mg (93%) of2-(2-carboxyethyl)-8-(5-N-Boc-aminopentynyl)-2,3,4,5-tetrahydro-1H-2-benzazepin-1-onemethyl ester as a colorless oil; ¹ H NMR(CDCl₃) d7.68(s, 1H), 7.37(d,J=6 Hz, 1H), 7.50(d, J=6 Hz, 1H), 4.7(brs, 1H), 3.84(t, J=6 Hz, 2H),3.71(s, 3H), 3.25(q, J=6 Hz, 4H), 2.73(t, J=6 Hz, 4H), 2.46(t, J=6 Hz,2H), 2.00(m, 2H), 1.78(m, 2H); ¹³ C NMR(CDCl₃) d171.38(CO), 170.49(CO),155.92, 136.83, 136.06, 133.61, 131.68, 128.25, 122.55, 89.55, 80.43,51.78, 47.18, 44.11, 39.75, 33.58, 29.92, 29.57, 28.72, 28.37, 16.88;MS(FAB) m/z=429.1(MH⁺).

b) A solution of2-(2-carboxyethyl)-8-(5-N-Boc-aminopentynyl)-2,3,4,5-tetrahydro-1H-2-benzazepin-1-onemethyl ester (66 mg, 0.154 mmol) in EtOH (1 mL) was treated withtrifluoroacetic acid (0.5 mL), and the resulting mixture stirred for 18hours. The volatiles were then removed, and the residue was dissolved intetrahydrofuran (1 mL), and treated with 50% NaOH (0.5 mL), and themixture was stirred for 20 minutes at room temperature. Trifluoroaceticacid was then added (3 mL), and the solution was concentrated in vacuo.The residue was purified by HPLC (1/2' C-18 reverse-phase column)eluting with a gradient of 3:7 methanol (0.1% trifluoroaceate)/water(0.1% trifluoroaceate), time 0 to 10 min, to 7:3 methanol(0.1%trifluoroaceate)/water(0.1% trifluoroaceate), time 10 to 40 min, toyield 46 mg (95%) of2-(2-carboxyethyl)-8-(5-aminopentynyl)-2,3,4,5-tetrahydro-1H-2-benzazepin-1-one trifluoroacetate as a light brown solid; ¹ H NMR(D₂ O) d7.32(s,1H), 7.25(d, J=6 Hz, 1H), 7.00(d, J=6 Hz, 1H), 3.63(t, J=6 Hz, 2H),2.95(m, 4H), 2.58(t, J=6 Hz, 2H), 2.50(t, J=6 Hz, 2H), 2.38(t, J=6 Hz,2H), 1.80(m, 4H); MS(FAB) m/z=315(MH⁺).

EXAMPLE 23 ##STR57##2-(2-carboxyethyl)-8-(5-guanidinopentynyl)-2,3,4,5-tetrahydro-1H-2-benzazepin-1-onetrifluoroacetate

a) A solution of2-(2-carboxyethyl)-8-(5-aminopentynyl)-2,3,4,5-tetrahydro-1H-2-benzazepin-1-onetrifluoroacetate (20 mg, 0.063 mmol) in saturated aqueous KHCO₃ (1 mL)was treated with formamidine sulfonic acid (80 mg, 1.0 mmol), and theresulting mixture stirred for 2 hours. The mixture was then treated withacetic acid, and the volatiles were removed. The residue was purified byHPLC (1/2' C-18 reverse-phase column) eluting with a gradient of 3:7methanol (0.1% trifluoroacetate)/water (0.1% trifluoroaceate), time 0 to10 min, to 7:3 methanol(0.1% trifluoroaceate)/water(0.1%trifluoroaceate), time 10 to 40 min, to yield 4.5 mg (15%) of2-(2-carboxyethyl)-8-(5-guanidinopentynyl)-2,3,4,5-tetrahydro-1H-2-benzazepin-1-onetrifluoroacetate as a light brown solid; ¹ H NMR(D₂ O) d7.40(s, 1H),7.25(dd, J=3, 6 Hz, 1H), 7.15(d, J=6 Hz, 1H), 3.80(t, J=6 Hz, 2H),3.30(m, 4H), 3.15(t, J=6 Hz, 2H), 2.00(t, J=6 Hz, 2H), 1.80(m, 2H);MS(FAB) m/z=357.1(MH⁺).

EXAMPLE 24 ##STR58##2-(2-carboxyethyl)-8-(4-(2-aminoethoxy)phenyl)-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-onetrifluoroacetate

a) A solution of 1-aminopropylene (10.6 grams, 0.186 mol) in methanolwas added to a methanolic solution of 3-phenylpropyleneoxide (5.07grams, 0.037 mol) and the mixture heated to reflux for 30 minutes. Themixture was allowed to warm to room temperature and concentrated invacuo to yield 7.2 grams (99%) of N-allyl-3-phenyl-2-hydroxypropylamine.¹ H NMR (CDCl₃, dTMS) 7.34-7.18 (5H, m, Ar-H), 5.84 (1H, ddt, ³ J_(HH)=17.1 Hz, ³ J_(HH) =10.2 Hz, ³ J_(HH) =6 Hz, CH₂ CH), 5.2-5.0 (2H, m,CH═CH₂), 3.86 (1H, m, CHOH), 3.19 (2H, m, NCH₂ CH═CH₂), 2.76-2.66 (3H,m, NCH₂ CH(OH)CHHPh), 2.50 (1H, dd ² J_(HH) =12 Hz, ³ J_(HH) =9 Hz). ¹³C NMR (CDCl₃) 138.4, 136.5, 129.3, 128.4, 126.3, 116.0, 70.6, 54.0,51.9, 41.7.

Using the above procedure, but substituting the appropriate alkenyloxideor allyl amine for 3-phenylpropyleneoxide or 1-aminopropylene,respectively, there may be prepared, for example, the followingcompounds:

N-allyl-2-hydroxypropylamine,N-(3-but-1-ene)-3-phenyl-2-hydroxypropylamine,N-(3-but-1-ene)-2-hydroxypropylamine.

b) To a magnetically stirred suspension of 5-iodosalisylic acid(Aldrich, 8.5 grams, 0.032 mol), was added oxalyl chloride (8.6 grams,0.064 mol) and one drop of dimethylformamide. The mixture was stirreduntil effervescence had ceased and concentrated in vacuo. The resultingresidue was diluted with diethyl ether and added to a solution ofN-allyl-3-phenyl-2-hydroxypropylamine (6.4 grams, 0.034 mol) in diethylether over a period of 30 minutes. The reaction was stirred for 1 hour,filtered, and concentrated in vacuo. the resulting residue was dissolvedin methylene chloride and washed with 1N HCl, sat. sodium bicarbonate,dried over sodium sulfate, filtered and concentrated in vacuo to yield12.26 grams (87%) ofN-allyl-N-(2-hydroxy-5-iodobenzoyl)-2-hydroxy-3-phenylpropylamine. Thematerial was used without further purification.

Using the above procedure, but substituting the appropriatehydroxypropylamine for N-allyl-3-phenyl-2-hydroxypropylamine there maybe prepared, for example, the following compounds:

N-allyl-N-(2-hydroxy-5-iodobenzoyl)-2-hydroxypropylamine,

N-(3-but-1-ene)-N-(2-hydroxy-5-iodobenzoyl)-2-hydroxy-3-phenylpropylamine,

N-(3-but-1-ene)-N-(2-hydroxy-5-iodobenzoyl)-2-hydroxypropylamine.

c) To a magnetically stirred solution ofN-allyl-N-(2-hydroxy-5-iodobenzoyl)-2-hydroxy-3-phenylpropylamine (12.05grams, 0.027 mol) in 100 mL THF was added triphenylphosphine (7.24grams, 0.027 mol), and diethyl azodicarboxylate (4.7 grams, 0.027 mol).The mixture was heated to reflux overnight, allowed to cool to roomtemperature, and concentrated in vacuo. the resulting residue wasdissolved in ethyl acetate (10 mL) and diluted with diethyl ether. Thesolids that form were filtered and the mother liquor was concentrated invacuo. The yellow oil was purified by column chromatography (SiO₂, using15% diethyl ether/85% hexane to 1:1 diethyl ether/hexane as the elutingsolvent gradient, Rf(product, 1:1 Et2O/heaxane)=0.64) to yield 4.31grams (38%) of2-allyl-4-benzyl-8-iodo-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-one.¹ H NMR (CDCl₃, dTMS) 8.10 (1H, d, ⁴ J_(HH) =2 Hz, C9-H), 7.69 (1H, dd,⁴ J_(HH) =2 Hz, ³ J_(HH) =9 Hz, C7-H), 7.4-7.2 (5H, m, C₆ H₅), 6.76 (1H,d, ³ J_(HH) =9 Hz, C6-H), 5.79 (1H, ddt, ³ J_(HH) =17 Hz, ³ J_(HH) =11Hz, ³ J_(HH) =6 Hz, CH₂ CH═CH₂), 5.2-5.0 (2H, m, CH═CH₂), 5.71 (1H, m,CHOH), 4.31 (1H, ddt, ² J_(HH) =15 Hz, ³ J_(HH) =6 Hz, ⁴ J.sub. HH =1Hz, NCHHCH═CH₂), 4.00 (1H, ddt, ² J_(HH) =15 Hz, ³ J_(HH) =6 Hz, ⁴J_(HH) =1 Hz, NCHHCH═CH₂), 3.34 (1H, dd, ² J_(HH) =16 Hz, ³ J_(HH) =5.1Hz, C3-H), 3.25 (1H, dd, ² J_(HH) =16 Hz, ³ J_(HH) =4.2 Hz, C3-H), 3.09(1H, dd, ² J_(HH) =14 Hz, ³ J_(HH) =7 Hz, CHHPh), 2.73 (1H, dd, ² J_(HH)=14 Hz, ³ J_(HH) =7 Hz, CHHPh). ¹³ C NMR (CDCl₃) 166.9, 152.7, 141.4,139.6, 136.5, 132.6, 129.8, 129.1, 128.8, 127.0, 124.6, 118.4, 86.7,84.7, 50.4, 48.9, 38.9. IR (NaCl, cm⁻¹) 1641, 1589, 1463, 1430, 1264,1217, 699.

Using the above procedure, but substituting the appropriatehydroxypropylamine forN-allyl-N-(2-hydroxy-5-iodobenzoyl)-2-hydroxy-3-phenylpropylamine theremay be prepared, for example, the following compounds:

2-allyl-4-methyl-8-iodo-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-one,

2-(3-but-1-ene)-4-benzyl-8-iodo-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-one,

2-(3-but-1-ene)-4-methyl-8-iodo-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-one.

d) To a magnetically stirred solution of2-allyl-4-benzyl-8-iodo-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-one(0.9234 grams, 2.2 mmol) in 4 mL THF at room temperature under anatmosphere of nitrogen was added 6.0 mL of a 0.5M solution of9-borabicylo[3.3.1]nonane in THF (3 mmol) and the mixture stirred for 1hour. The reaction was quenched with 6 mL of a solution of 2 grams ofsodium hydroxide and 22 mL of a 1:1 mixture of ethanol and water. To theresulting solution was added 7 mL of a 30% solution hydrogen peroxide inwater. After 30 minutes the mixture was partitioned between diethylether and water. The organic layer was washed with 10% citric acid andbrine, dried over sodium sulfate, concentrated in vacuo, and purified bycolumn chromatography (SiO2, using 1:5 ethyl acetate/methylene chlorideas the eluting solvent, R_(f) (product)=0.22) to yield 0.74 grams (77%)of2-(3-hydroxypropyl)-4-benzyl-8-iodo-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-one.1H NMR (CDCl₃, dTMS) 8.08 (1H, d, ⁴ J_(HH) =2 Hz, C9-H), 7.71 (1H, dd, ⁴J_(HH) =2 Hz, ³ J_(HH) =8 Hz, C7-H), 7.4-7.2 (5H, m, C₆ H₅), 6.78 (1H,d, ^(3J) _(HH) =8 Hz, C6-H), 4.64 (1H, m, ArOCH), 3.70 (2H, m, CH₂ OH),3.58 (2H, bt, ³ J_(HH) =5 Hz, NCH₂ CH₂), 3.39 (1H, dd, ² J_(HH) =15 Hz,³ J_(HH) =8 Hz, C3-H), 3.24 (1H, dd, ² J_(HH) =15 Hz, ³ J_(HH) =3 Hz,C3-H), 3.1 (1H. dd, ² J_(HH) =14 Hz, ³ J_(HH) =7 Hz, CHHPh), 2.76 (1H,dd, ² J_(HH) =14 Hz, ³ J_(HH) =7 Hz, CHHPh), 1.68 (2H, m, CH₂ CH₂ OH).¹³ C NMR (CDCl₃) 168.3, 152.6, 141.6, 139.4, 136.2, 132.1, 131.9, 129.2,129.0, 128.8, 128.4, 127.0, 124.7, 86.8, 85.7, 58.0, 49.9, 44.5, 38.8,30.3. IR (NaCl, cm⁻¹) 3422 (b), 1636, 1463, 1436, 1217, 1064.

Using the above procedure, but substituting the appropriate5-oxa-2-benzazepin-1-one for2-allyl-4-benzyl-8-iodo-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-onethere may be prepared, for example, the following compounds:

2-(3-hydroxypropyl)-4-methyl-8-iodo-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-one,

2-(4-hydroxybut-2-yl)-4-benzyl-8-iodo-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-one,

2-(4-hydroxybut-2-yl)-4-methyl-8-iodo-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-one.

e) To a magnetically stirred solution of2-(3-hydroxypropyl)-4-benzyl-8-iodo-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-one(0.75 grams, 1.7 mmol) in 5 mL dimethylformamide at room temperature wasadded a solution of pyridinium dichromate (2.58 grams, 6.86 mmol) in 5mL dimethylformamide. The reaction mixture was stirred overnight,diluted with 75 mL water, washed 3×75 mL diethyl ether, made acidic to apH of 2 with conc. HCl and extracted 3×75 mL diethyl ether. The combinedorganics were extracted 3×40 mL 1N sodium hydroxide. The combinedaqueous layers were acidified to a pH of 2 with canc HCl and extracted3×50 mL diethyl ether. These ether layers were combined and dried overmagnesium sulfate, filtered, and concentrated in vacuo to yield 0.557grams (73%) of2-(2-carboxyethyl)-4-benzyl-8-iodo-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-one.¹ H NMR (CDCl₃, dTMS) 8.07 (1H, d, ⁴ J_(HH) =2 Hz, C9-H), 7.69 (1H, dd,⁴ J_(HH) =2 Hz, ³ J_(HH) =8 Hz, C7-H), 7.4-7.2 (5H, m, C₆ H₅), 6.75 (1H,d, ³ J_(HH) =8 Hz, C6-H), 4.75 (1H, m, ArOCH), 3.89 (1H, dt, ² J_(HH)=14 Hz, ³ J_(HH) =6 Hz, NCHHCH₂ CO₂), 3.69 (1H, dt, ² J_(HH) =14 Hz, ³J_(HH) =6 Hz, NCHHCH₂ CO₂), 3.44 (2H, d, ³ J_(HH) =3 Hz, CH₂ Ph), 3.07(1H, dd, ² J_(HH) =14 Hz, ³ J_(HH) =7 Hz, C3-H), 2.8-2.7 (3H, m, C3-H,CH₂ CO₂). ¹³ C NMR (CDCl3) 176.1, 167.6, 164.4, 152.8, 141.7, 139.5,136.4, 129.4, 129.1, 128.9, 128.8, 127.0, 124.7, 86.7, 84.7, 51.4, 45.0,38.8, 33.0.

Using the above procedure, but substituting the appropriate5-oxa-2-benzazepin-1-one for2-(3-hydroxypropyl)-4-benzyl-8-iodo-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-onethere may be prepared, for example, the following compounds:

2-(2-carboxyethyl)-4-methyl-8-iodo-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-one,

2-(3-carboxy-2-propyl)-4-benzyl-8-iodo-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-one,

2-(3-carboxy-2-propyl)-4-methyl-8-iodo-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-one.

f) A solution of diazomethane in ether, prepared by allowing a slurry of2.98 grams of N-nitroso-N-methylurea and 10 mL ether to react with asolution of 20 grams of KOH in 20 mL water, was carefully added via apipet to solution of2-(2-carboxyethyl)-8-iodo-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-one(0.42 grams, 0.93 mmol) in 20 mL diethyl ether until yellow colorpersists. The mixture was allowed to stand overnight and concentrated invacuo. The resulting residue was purified by column chromatography(SiO2, 1:9 ethyl acetate/hexane, R_(f) (product)=0.2) to yield 0.275grams (64%) of2-(2-carboxyethyl)-8-iodo-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-onemethyl ester. ¹ H NMR (CDCl₃, dTMS) 8.06 (1H, d, ⁴ J_(HH) =2 Hz, C9-H),7.68 (1H, dd, ⁴ J_(HH) =2 Hz, ³ J_(HH) =8 Hz, C7 -H), 7.4-7.2 (5H, m, C₆H₅), 6.75 (1H, d, ³ J_(HH) =8 Hz, C6-H), 4.76 (1H, m, ArOCH), 3.88 (1H,dt, ² J_(HH) =14 Hz, ³ J_(HH) =6 Hz, NCHHCH₂ CO₂), 3.69 (4H, m, NCHHCH₂CO₂ CH₃), 3.44 (2H, m, C3-H), 3.06 (1H, dd, ² J_(HH) =14 Hz, ³ J_(HH) =7Hz, C3-H), 2.76 (1H, dd, ² J_(HH) =14 Hz, ³ J_(HH) =7 Hz, CHHPh), 2.69(2H, m, CHHPh, CH₂ CO₂). ¹³ C NMR (CDCl3) 172.4, 167.2, 164.4, 152.6,141.4, 139.4, 136.5, 129.6, 129.1, 121.0, 128.8, 127.0, 124.6, 86.6,84.7, 51.8, 51.3, 45.1, 38.7, 33.0.

Using the above procedure, but substituting the appropriate5-oxa-2-benzazepin-1-one for2-(2-carboxyethyl)-8-iodo-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-onethere may be prepared, for example, the following compounds:

2-(2-carboxyethyl)-4-methyl-8-iodo-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-onemethyl ester,

2-(3-carboxy-2-propyl)-4-benzyl-8-iodo-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-onemethyl ester,

2-(3-carboxy-2-propyl)-4-methyl-8-iodo-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-onemethyl ester.

g) To a magnetically stirred solution of 4-iodophenol (15 grams, 0.068mol) in 100 mL THF was sequentially added triphenylphosphine (19.67grams, 0.075 mol), diethyl azodicarboxylate (13.06 grams, 0.073 mol),and 2-azidoethanol (5.93 grams, 0.068 mol). The mixture was stirredovernight, concentrated in vacuo, diluted with 90 mL ethyl acetate anddiluted with hexane (400 mL), and the resulting solids filtered away.The filtrate was concentrated in vacuo, diluted with diethyl ether, andextracted with 1N NaOH and water. Pentane was added to induceprecipatation of a white solid that was again filtered away. The fitratewas concentrated in vacuo, and dissolved in methanol (60 mL).Triethylamine (27 grams, 0.267 mol) and propanedithiol (23 grams, 0.215mol) were added and the mixture stirred at room temperature overnight.The solution was diluted with 100 mL water and partitioned betweenmethylene chloride and 1N NaOH. The organic layer was extracted with2×200 mL 1N HCl and the aqueous layer washed with 100 mL methylenechloride, made basic with 2N NaOH and extracted 3×75 mL methylenechloride. The combined organics were dried over sodium carbonate,filtered and concentrated in vacuo to yield 12.97 grams of2-(4-iodophenoxy)ethyl amine (72%). ¹ H NMR (CDCl₃, dTMS) 7.56 (2H, d, ³J_(HH) =9 Hz, Ar-H), 6.63 (2H, d, ³ J_(HH) =9 Hz, Ar-H), 4.03 (2H, t, ³J_(HH) =5 Hz, CH₂ N₃), 3.57 (2H, t, ³ J_(HH) =5 Hz, OCH₂). ¹³ C NMR(CDCl₃) 158.0, 138.2, 116.9, 83.4, 66.9, 49.9. IR (NaCl, cm⁻¹) 2930,2107 (s), 1589, 1483, 1284, 1237, 1058, 819.

h) 2-(4-iodophenoxy)ethylamine (10 grams, 0.038 mol) dissolved in THF(50 mL) was allowed to react with di-t-butyl dicarbonate (9.13 grams,0.041 mol) at room temperature for 1 hour. The reaction mixture wasconcentrated in vacuo to yield 17.7 grams (99%) ofN-Boc-2-(4-iodophenoxy)ethylamine.

i) A slurry of2-(2-carboxyethyl)-4-benzyl-8-iodo-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-onemethyl ester (0.155 grams, 0.334 mmol),N-Boc-2-(4-iodophenoxy)ethylamine (0.246 grams, 0.664 mmol), degassedtriethylamine (2 mL), bis(triphenylphosphine)palladium dichloride (11mgs, 10 mol %), and coprous iodide (6 mgs, 20 mol %) was heated toreflux overnight. The reaction was concentrated in vacuo, trituratingthe resulting residue with diethyl ether (30 mL). The ethereal solutionwas concentrated in vacuo and the residue purified by columnchromatography (SiO₂, using 1:1 ethyl acetate/hexane to ethyl aceate asthe eluting solvent gradient, R_(f) (product)=0.08) to yield 19.1 mgs(10%) of2-(2-carboxyethyl)-4-benzyl-8-(4-(2-N-Boc-amino)ethoxyphenyl)-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-onemethyl ester. 1H NMR (CDCl₃, dTMS) 7.94 (1H, d, ⁴ J_(HH) =2 Hz, C9-H),7.59 (1H, dd, ⁴ J_(HH) =2 Hz, ³ J_(HH) =8 Hz, C7-H), 7.52 (2H, d, ³J_(HH) =9 Hz, C8-o-Ar-H), 7.40-7.25 (5H, m, C₆ H₅), 7.05 (1H, d, ³J_(HH) =8 Hz, C6-H), 6.96 (2H, d, ³ J_(HH) =9 Hz, C8-m-Ar-H), 5.03 (1H,bs, NH), 4.76 (1H, m, OCH), 4.06 (2H, t, ³ J_(HH) =5 Hz, OCH₂ CH₂ N),3.92 (1H, dt, ² J_(HH) =14 Hz, ³ J_(HH) =7 Hz, NCHHCH₂ CO₂), 3.73 (1H,dt, ² J_(HH) =14 Hz, ³ J_(HH) =7 Hz, NCHHCH₂ CO₂), 3.67 (3H, s, CH₃),3.56 (2H, bq, .sup. 3 J_(HH) =6 Hz, CH₂ NH), 3.51 (1H, dd, ² J_(HH) =16Hz, ³ J_(HH) =8 Hz, C3-H), 3.43 (1H, dd, ² J_(HH) =16 Hz, ³ J_(HH) =5Hz, C3-H), 3.12 (1H, dd, ² J_(HH) =14 Hz, ³ J_(HH) =7 Hz, CHHPh), 2.78(1H, dd, ² J_(HH) =14 Hz, ³ J_(HH) =7 Hz, CHHPh), 2.72 (2H, m, CH₂ CO₂),1.48 (9H, s, Bu^(t)), ¹³ C NMR (CDCl3) 172.6, 168.9, 136.8, 136.5,130.8, 129.1, 128.8, 128.7, 128.3, 126.9, 123.0, 114.8, 84.6, 60.4,51.8, 51.5, 45.0, 38.8, 33.2, 28.3.

Using the above procedure, but substituting the appropriate5-oxa-2-benzazepin-1-one for2-(2-carboxyethyl)-8-iodo-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-onethere may be prepared, for example, the following compounds:

2-(2-carboxyethyl)-4-methyl-8-(4-(2-N-Boc-amino)ethoxyphenyl)-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-onemethyl ester,

2-(3-carboxy-2-propyl)-4-benzyl-8-(4-(2-N-Boc-amino)ethoxyphenyl)-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-onemethyl ester,

2-(3-carboxy-2-propyl)-4-methyl-8-(4-(2-N-Boc-amino)ethoxyphenyl)-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-onemethyl ester,

2-(2-carboxyethyl)-4-benzyl-8-[4-(4-N-Boc-piperazine)phenyl]-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-onemethyl ester,

2-(2-carboxyethyl)-4-methyl-8-[4-(4-N-Boc-piperazine)phenyl]-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-onemethyl ester,

2-(3-carboxy-2-propyl)-4-benzyl-8-[4-(4-N-Boc-piperazine)phenyl]-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-onemethyl ester,

2-(3-carboxy-2-propyl)-4-methyl-8-[4-(4-N-Boc-piperazine)phenyl]-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-onemethyl ester,

2-(2-carboxyethyl)-4-benzyl-8-[4-(4-N-Boc-aminomethyl)phenyl]-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-onemethyl ester,

2-(2-carboxyethyl)-4-methyl-8-[4-(4-N-Boc-aminomethyl)phenyl]-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-onemethyl ester,

2-(3-carboxy-2-propyl)-4-benzyl-8-[4-(4-N-Boc-aminomethyl)phenyl]-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-onemethyl ester,

2-(3-carboxy-2-propyl)-4-methyl-8-[4-(4-N-Boc-aminomethyl)phenyl]-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-onemethyl ester.

j) To a solution of2-(2-carboxyethyl)-4-benzyl-8-(4-(2-N-Boc-amino)ethoxyphenyl)-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-onemethyl ester (19.1 mgs, 0.03 mmol) in 0.5 mL acetonitrile and 0.5 mLwater was added a concentrated solution of HCl in ethyl acetate (1 mL)and the reaction allowed to stand for 15 minutes, concentrated in vacuo,dissolved in methanol (1 mL) and allowed to react with 2N NaOH (1 mL).The reaction was quenched with acetic acid (0.5 mL) and concentrated invacuo, dissolved in a minimum of water and purified by high-pressurecolumn chromatography (HPLC, 1/2" reverse-phase C-18 column, 1:4acetonitrile(0.1% TFA)/water (0.1% TFA) to 3:2 acetonitrile(0.1%TFA)/water (0.1% TFA) as the eluting solvent gradient) to yield 4.2 mgs(30%) of2-(2-carboxyethyl)-8-(4-(2-aminoethoxy)phenyl)-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-one.¹ H NMR (CD₃ OD) 7.80 (1H, d, ⁴ J_(HH) =2 Hz, C9-H), 7.67 (1H, dd, ⁴J_(HH) =2 Hz, ³ J_(HH) =8 Hz, C7-H), 7.58 (2H, d, ³ J_(HH) =9 Hz,C8-o-Ar-H), 7.40-7.35 (5H, m, C₆ H₅), 7.10 (2H, d, ³ J_(HH) =9 Hz,C8-m-Ar-H), 7.03 (1H, d, ³ J_(HH) =8 Hz, C6-H), 4.28 (2H, t, 3JHH=4 Hz,OCH₂ CH₂), 3.81 (2H, m, NCH₂ CH₂ CO₂), 3.61 (1H, dd, ² J_(HH) =14 Hz, ³J_(HH) =1 Hz, C3-H), 3.44 (1H, dd, ² J_(HH) =14 Hz, ³ J_(HH) =4 Hz,C3-H), 3.41 (2H, t, ³ J_(HH) =5 Hz, CH₂ Ph), 2.87 (2H, t, ³ J_(HH) =7Hz, CH₂ NH₂), 2.50 (2H, t, ³ J_(HH) =7 Hz, CH₂ CO₂). HRMS (FAB, MH⁺)m/z=461.2109 (cald for C₂₇ H₂₉ N₂ O₅ : 461.2076).

Using the above procedure, but substituting the appropriate5-oxa-2-benzazepin-1-one, for2-(2-carboxyethyl)-4-benzyl-8-(4-(2-N-Boc-amino)ethoxyphenyl)-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-onemethyl ester there may be prepared, for example, the followingcompounds:

2-(2-carboxyethyl)-4-methyl-8-(4-(2-amino)ethoxyphenyl)-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-one,

2-(3-carboxy-2-propyl)-4-benzyl-8-(4-(2-amino)ethoxyphenyl)-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-one,

2-(3-carboxy-2-propyl)-4-methyl-8-(4-(2-amino)ethoxyphenyl)-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-one,

2-(2-carboxyethyl)-4-benzyl-8-[4-(1-piperazine)phenyl]-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-one,

2-(2-carboxyethyl)-4-methyl-8-[4-(1-piperazine)phenyl]-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-one,

2-(3-carboxy-2-propyl)-4-benzyl-8-[4-(1-piperazine)phenyl]-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-one,

2-(3-carboxy-2-propyl)-4-methyl-8-[4-(1-piperazine)phenyl]-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-one,

2-(2-carboxyethyl)-4-benzyl-8-[4-(4-aminomethyl)phenyl]-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-one,

2-(2-carboxyethyl)-4-methyl-8-[4-(4-aminomethyl)phenyl]-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-one,

2-(3-carboxy-2-propyl)-4-benzyl-8-[4-(4-aminomethyl)phenyl]-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-one,

2-(3-carboxy-2-propyl)-4-methyl-8-[4-(4-aminomethyl)phenyl]-2,3,4,5-tetrahydro-1H-5-oxa-2-benzazepin-1-one.

EXAMPLE 25 Fibrinogen-GP II_(b) III_(a) Receptor ELISA Binding Assay

The method used is essentially that described in Nachman and Leung (J.Clin. Invest., 69: 263-269 [1982]). The GP II_(b) III_(a) is essentiallypurified as described in Fitzgerald et al., (Anal. Biochem. 151: 169-177[1985]).

A. GP II_(b) III_(a) Purification

Outdated human platelets are washed 3 times with 10 mM tris-HCl, 150 mMNaCl (TBS), 1 mM EDTA, pH 7.5, and centrifuged at 2000×g to pelletcells. Cells are lysed in 5 pellet volumes of TBS, 1% Triton X-100, 1 mMCa₂ Cl₂, and followed by centrifugation at 30,000×g. The supernatantfraction is collected and the supernatant is loaded onto aconcanavalin-A column, previously equilibrated in TBS, 1 mM Ca₂ Cl₂,0.1% Triton, 0.05% NaN₃ and eluted with 0.2M a-methylmannoside.Fractions are pooled and loaded onto a heparin-agarose column. Theflowthrough is collected and concentrated on an Amicon YM 30 filter to avolume of approximately 5-10 ml. The concentrate is then applied to anS-300 column (500 ml) and 6 ml fractions are collected. The GP II_(b)III_(a) containing fractions are collected, pooled, and stored at -80°C.

B. Purification of Low Solubility Fraction of Fibrinogen

The purification of fibrinogen is conducted essentially as described byLipinska et al., (J. Lab. Clin. Med. 507, [1974]). Briefly, a 0.3% w/vsolution of human fibrinogen (Kabi #5302) is dissolved in 150 mM NaCl.Saturated (NH₄)₂ SO₄ is added dropwise with stirring to the fibrinogensolution to obtain about 16% saturation. The precipitate is spun down inappropriate size bottles at 2000×g. The supernatant is decanted and theprecipitate resuspended in 150 mM NaCl (approximately 50% of theoriginal volume). NH₄ SO₄ is again added dropwise to obtain 16%saturation. The suspension is spun down and the precipitate isresuspended in Tris-saline in a minimal volume (approximately 5% of theoriginal volume). Any remaining insoluble material is spun down at 2000rpm in a Sorval type centrifuge and the fibrinogen supernatant isdecanted and dialyzed overnight at 4° C. against Tris-saline.Characterization of the fibrinogen is by the Bradford protein assay,SDS-PAGE, and/or Western blotting using well known standard procedures.

C. ELISA Assay

Briefly, 96 well plates are coated (Type Nunc 1 Maxisorp™) with 10 mg/mlpurified fibrinogen (100 ml/well), and allowed to stand overnight at 4°C. The plates are washed three times with PBS Tween (0.137 M NaCl,0.003M KCl, 0.008M Na₂ HPO₄, 0.001M KH₂ PO₄, pH 7.4 at room temperature,0.05% Tween-20) and blocked for 1 to 2 hours at room temperature with200 ml/well TNCNT (which is 0.5% BSA, 20 mM Tris, pH 7.5 at roomtemperature, 120 mM NaCl, 0.2% NaN₃, 2 mM CaCl₂, 0.05% Tween 20, 0.5%BSA [Calbiochem RIA grade or better]) on a plate shaker. The plates areagain washed three times with PBS/Tween and then 50 ml of sample inTNCNT is added. The mixture is incubated for 15 minutes at roomtemperature on a plate shaker. The stock solution of purified GP II_(b)III_(a) receptor from human platelets, (0.4-1.0 mg/ml GP II_(b) III_(a)in 0.1% Triton X-100, 1 mM CaCl.sub. 2, 20 mM Tris, 150 mM NaCl, 0.05%NaN₃ in 0.3M N-acetyl glucosamine pH 7.5, stored at -70° C.), isreconstituted to about 40 mg/ml in TNCNT. Fifty ml of this diluted GPII_(b) III_(a) is then added to each well and incubated on a plateshaker at room temperature. After one hour, the plates are washed fourtimes with PBS/Tween and 100 ml of a polyclonal or monoclonal antibodyspecific for GP IIIa such as AP3 (1 mg/ml) (See e.g. Newman et al.,Blood, 65: 227-232 [1985]) in ELISA buffer (PBS, 0.5% BSA, 0.05% Tween20, 0.01% Thimerasol) is added. After a one hour incubation at roomtemperature on a plate shaker, the samples are washed 4 times withPBS/Tween. One hundred ml of GAM-HRP (horse radish peroxidase conjugateof goat anti-mouse IgG [Pel-Freeze Cat. 715305-1] dissolved in ELISAbuffer) previously diluted to 1:10,000 is then added and the samples areincubated 1 hour at room temperature on a plate shaker. The samples arethen washed 4 times with PBS/Tween and 100 ml OPD/H₂ O₂ substrate isadded (OPD/H₂ O₂ substrate: 10 mg o-phenylenediamine in 15 mlphosphate/citrate buffer, at room temperature and covered with foil;just before use, 6.25 ml of 30% H₂ O₂ is added to give a final solutionof 0.67 mg OPD/ml in 0.0125% H₂ O₂). (The phosphate/citrate bufferconsists of 16 mM Citric Acid, 50 mM Na₂ HPO₄, pH 5.0). The colordevelops within about 3 to 20 minutes and the reaction is stopped with100 ml 1M H₂ SO₄. The optical density at 492 nm vs 405 nm is recordedand IC₅₀ values are determined.

EXAMPLE 26 Human Vitronectin-Vitronectin Receptor (a_(v) b₃) ELISA Assay

A. Human Vitronectin Purification

Human vitronectin (Vn) is isolated from human plasma and purified byaffinity chromatography by the method of Yatohgo et. al., (CellStructure and Function 13: 281-292 [1988]).

B. Human Vitronectin receptor (a_(v) b₃) Purification

Human vitronection receptor (VnR) is purified from human placenta by themethod of Pytela et al., (Methods Enzymol., 144: 475 [1987]).Alternatively the a_(v) b₃ receptor can be purified from some cell lines(e.g., human embryonic kidney 293 cells) transfected with DNA sequencesfor both the a_(v) and b₃ subunits. The subunits are purified byemploying octylglucoside extraction followed by Con-A,Heparin-Sepharose, and S-300 Chromatography.

C. Monoclonal Antibodies

Anti-GP II_(b) III_(a) monoclonal antibodies specific for human GPIII_(a) are prepared by the method of Newman et al. (Blood, 65: 227-232[1985]), or a similar procedure. This mouse Mab is specific for the b₃subunit of the vitronectin receptor.

Rabbit Fab 2 anti-mouse Fc fragment horse radish peroxidase conjugate(anti-MuFc HRP) is obtained from PelFreeze (cat. no. 715305-1).

D. ELISA Assay

Maxisorp microtiter plates are coated with 2 mg/ml human vitronectindissolved in PBS (50 ml/well) and stored overnight at 4° C. The platesare washed two times with PBS-0.05% Tween-20 (wash buffer) and blockedby incubating with about 150 ml/well of assay buffer (1%, BSA [RIA gradeor better] in 50 mM Tris-HCl, 100 mM NaCl, 1 mM MgCl₂, CaCl₂, MnCl₂ pH7.4) for 60 minutes. Dilutions of standards are prepared and putativeinhibitors (Table 3) are dissolved in assay buffer. The blocked platesare emptied and 25 ml/well of inhibitor or standard solution is added toeach well. Twenty-five ml of a 30 mg/ml solution of purified a_(v) b₃ inassay buffer is pipetted into the coated plate. The final concentrationof receptor in the assay well is about 15 mg/ml. The plate is incubatedon a shaker for 60 minutes. Meanwhile, for each microtite plate, 6 mlbuffer solution containing 1.5 mg/ml of mouse monoclonal antibodyspecific for b₃ is prepared. To this solution is added ml of thesecondary antibody, which is anti-mouse-Fc-HRP antibody conjugate. Forexample, for one plate, prepare 6 ml of a 1.5 mg/ml mouse Mab solutionto which is added 1 ml of anti-mouse-Fc-HRP antibody stock, (thisrepresents a 1:6000 dilution of the antibody-HRP conjugate). Thismixture is allowed to incubate during the receptor-inhibitor incubation.The assay plates are washed 4 times with PBS-Tween and 50 ml/well of theantibody mixture is then pipetted into the plate for a 60 minuteincubation. The plate is washed 4 times and the color reaction isdeveloped with 50 ml/well of 0.67 mg/ml o-phenyldiamine in PBScontaining 0.012% H₂ O₂. Alternatively, 16 mM citric acid, 50 mM Na₂ PO₄at pH 5.0 can be used as a substrate buffer. The reaction is stoppedwith 50 ml/well 1 M H₂ SO₄. The plates are read at 492-405 nm and thedata analyzed by four-parameter fit.

EXAMPLE 27 GP II_(b) III_(a) -von Willebrand factor (vWF) ELISA Assay

A. ELISA Assay

Microtiter plates are coated with 1.0 mg/ml GP II_(b) III_(a), preparedby the method of Fitzgerald et al., (Anal. Biochem. 151: 169-177 [1985])and allowed to incubate overnight in coat buffer. The plates are thenwashed three times in wash buffer (0.05% Tween 20 in PBS) and 150 ml ofassay buffer is added and allowed to incubate for 1-2 hours at roomtemperature on plate shaker. The plates are washed three times and 50 mlof 2x inhibitor in assay buffer (Assay buffer: 0.5% BSA/50 mM Tris, 100mM NaCl, 1.0 mM CaCl₂, 1.0 mM MgCl₂, 1.0 mM MnCl₂ ; coat buffer is thesame but without BSA) is added. Fifty ml of 4.0 mg/ml vWF (prepared asdescribed by Ledford et al., Thrombosis and Haemostasis, 64(4): 569-575]1990]) in assay buffer is then added and allowed to incubate for onehour at room temperature on plate-shaker. The plates are washed threetimes and the antibody mixture is added (1:5000 of mouse anti-vWF and1:5000 of rabbit-anti-mouse-Fc-HRP, both commercially available) inassay buffer and incubated for 1 hour at room temperature onplate-shaker. Plates are again washed three times and 100 ml ofsubstrate solution (10 mg OPD, 6.5 ml H₂ O₂, 15 ml phosphate citratebuffer) is added and incubated at room temperature. The color change ofOPD/H₂ O₂ reagent is read at 492 nm with a 405 nm reference wavelengthon the filter photometer.

EXAMPLE 28 In Vitro Human Platelet Aggregation Assay

Platelet aggregation assays are performed in human platelet rich plasma(PRP). Fifty milliliters of whole human blood (9 parts) is drawn on 3.6%sodium citrate (1 part) from a donor who has not taken aspirin orrelated medications for at least two weeks. The blood is centrifuged at160×g for 10 minutes at 22° C. and allowed to stand for 5 minutes afterwhich the PRP is decanted. Platelet poor plasma (PPP) is isolated fromthe remaining blood after centrifugation at 2000×g for 25 minutes. Theplatelet count of the PRP is diluted to about 300,000 platelets permicroliter with PPP.

A 225 ml aliquot of PRP plus 25 ml of either a dilution of the testinhibitor sample or a control (PBS) is incubated for 5 minutes in aChrono-log Whole Blood Aggregometer at 25° C. An aggregating agent(collagen, 1 mg/ml; U46619, 100 ng/ml; or ADP, 17 mM) is added and thetransmission is recorded.

EXAMPLE 29 Results of ELISA Assays for 1, 3, 4, and 7 substitutedBenzodiazepinediones

    __________________________________________________________________________     ##STR59##                                                                                                           IC.sub.50                              Cmpd #                                                                             Q.sup.1                                                                              L.sup.1   R.sup.22 R.sup.20                                                                          D   Fg/IIbI                                __________________________________________________________________________     1   amine  (CH.sub.2).sub.3                                                                        H        H   H   8.3                                     2   guanidine                                                                            (CH.sub.2).sub.3                                                                        H        H   H   0.714                                   3   amine  (CH.sub.2).sub.3                                                                        CH.sub.3 H   H   28.0                                    4   guanidine                                                                            (CH.sub.2).sub.3                                                                        CH.sub.3 H   H   0.466                                   5   amine  CH.sub.2 CC                                                                             CH.sub.3 H   H   7.0                                     6   guanidine                                                                            CH.sub.2 CC                                                                             CH.sub.3 H   H   0.170                                   7   amine  (CH.sub.2).sub.3                                                                        CH.sub.3 CH.sub.3                                                                          H   30.0                                    8   guanidine                                                                            (CH.sub.2).sub.3                                                                        CH.sub.3 CH.sub.3                                                                          H   >100.0                                  9   amine  CH.sub.2 CC                                                                             CH.sub.3 CH.sub.3                                                                          H   70.0                                   10   guanidine                                                                            CH.sub.2 CC                                                                             CH.sub.3 CH.sub.3                                                                          H   30.0                                   11   amine  (CH.sub.2).sub.3                                                                        CH.sub.3 Ph  H   600.0                                  12   guanidine                                                                            (CH.sub.2).sub.3                                                                        CH.sub.3 Ph  H   2.30                                   13   amine  CCCH.sub.2                                                                              CH.sub.3 Ph  H   >1000.0                                14   guanidine                                                                            CCCH.sub.2                                                                              CH.sub.3 Ph  H   25.0                                   15   amine  (CH.sub.2).sub.3                                                                        CH.sub.3 (CH.sub.2).sub.2                                                                      >100.0                                 16   guanidine                                                                            (CH.sub.2).sub.3                                                                        CH.sub.3 (CH.sub.2).sub.2                                                                      >100.0                                 17   amine  (CH.sub.2).sub.3                                                                        CH.sub.3 (CH.sub.2).sub.2                                                                      >100.0                                 18   guanidine                                                                            (CH.sub.2).sub.3                                                                        CH.sub.3 (CH.sub.2).sub.2                                                                      >100.0                                 19   amine  (CH.sub.2).sub.4                                                                        CH.sub.3 H   H   5.0                                    20   guanidine                                                                            (CH.sub.2).sub.4                                                                        CH.sub.3 H   H   0.250                                  21   amine  (CH.sub.2).sub.2 CC                                                                     CH.sub.3 H   H   6.0                                    22   guanidine                                                                            (CH.sub.2).sub.2 CC                                                                     CH.sub.3 H   H   0.140                                  23   amine  (CH.sub.2).sub.4                                                                        CH.sub.3 CH.sub.3                                                                          H   >100.0                                 24   guanidine                                                                            (CH.sub.2).sub.4                                                                        CH.sub.3 CH.sub.3                                                                          H   100.0                                  25   amine  (CH.sub.2).sub.2 CC                                                                     CH.sub.3 CH.sub.3                                                                          H   >100.0                                 26   guanidine                                                                            (CH.sub.2).sub.2 CC                                                                     CH.sub.3 CH.sub.3                                                                          H   80.0                                   27   amine  (CH.sub.2).sub.5                                                                        CH.sub.3 H   H   1.9                                    28   guanidine                                                                            (CH.sub.2).sub.5                                                                        CH.sub.3 H   H   0.055                                  29   amine  (CH.sub.2).sub.5                                                                        H        H   H   2.92                                   30   guanidine                                                                            (CH.sub.2).sub.5                                                                        H        H   H   0.204                                  31   amine  (CH.sub.2).sub.3 CC                                                                     H        H   H   1.43                                   32   guanidine                                                                            (CH.sub.2).sub.3 CC                                                                     H        H   H   0.254                                  33   amine  (CH.sub.2).sub.3 CC                                                                     CH.sub.3 H   H   0.096                                  34   guanidine                                                                            (CH.sub.2).sub.3 CC                                                                     CH.sub.3 H   H   0.0036                                 35   amine  (CH.sub.2).sub.3 CC                                                                     CH.sub.2 (mNO.sub.2 C.sub.6 H.sub.4)                                                   H   H   0.013                                  36   guanidine                                                                            (CH.sub.2).sub.3 CC                                                                     CH.sub.2 (mNO.sub.2 C.sub.6 H.sub.4)                                                   H   H   0.0032                                 37   amine  (CH.sub.2).sub.3 CC                                                                     CH.sub.3 H   CH.sub.3                                                                          0.061                                  38   guanidine                                                                            (CH.sub.2).sub.3 CC                                                                     CH.sub.3 H   CH.sub.3                                                                          0.018                                  39   amine  (CH.sub.2).sub.6                                                                        CH.sub.3 H   H   0.070                                  40   guanidine                                                                            (CH.sub.2).sub.6                                                                        CH.sub.3 H   H   0.120                                  41   amine  (CH.sub.2).sub.4 CC                                                                     CH.sub.3 H   H   0.100                                  42   guanidine                                                                            (CH.sub.2).sub.4 CC                                                                     CH.sub.3 H   H   0.060                                  43   amine  p(CH.sub.2)C.sub.6 H.sub.4 CC                                                           CH.sub.3 H   H   0.012                                  44   guanidine                                                                            p(CH.sub.2)C.sub.6 H.sub.4 CC                                                           CH.sub.3 H   H   0.012                                  45   amine  p(CH.sub.2)C.sub.6 H.sub.4 (CH.sub.2).sub.2                                             CH.sub.3 H   H   0.085                                  46   guanidine                                                                            p(CH.sub.2)C.sub.6 H.sub.4 (CH.sub.2).sub.2                                             CH.sub.3 H   H   0.265                                  47   amine  mC.sub.6 H.sub.4 (CH.sub.2).sub.2                                                       CH.sub.3 H   H   10.0                                   48   bis-guanidine                                                                        mC.sub.6 H.sub.4 (CH.sub.2).sub.2                                                       CH.sub.3 H   H   3.0                                    49   amine  mC.sub.6 H.sub.4 CC                                                                     CH.sub.3 H   H   6.0                                    50   bis-guanidine                                                                        mC.sub.6 H.sub.4 CC                                                                     CH.sub.3 H   H   25.0                                   51   amine  (CH.sub.2).sub.6                                                                        CH.sub.3 H   Ph  0.200                                  52   guanidine                                                                            (CH.sub.2).sub.6                                                                        CH.sub.3 H   Ph  0.390                                  53   amine  (CH.sub.2).sub.4 CC                                                                     CH.sub.3 H   Ph  0.240                                  54   guanidine                                                                            (CH.sub.2).sub.4 CC                                                                     CH.sub.3 H   Ph  0.100                                  55   amine  (CH.sub.2).sub.4 CC                                                                     CH.sub.2 (mNO.sub.2 C.sub.6 H.sub.4)                                                   H   H   0.008                                  56   guanidine                                                                            (CH.sub.2).sub.4 CC                                                                     CH.sub.2 (mNO.sub.2 C.sub.6 H.sub.4)                                                   H   H   0.006                                  57   nitrile                                                                              pC.sub.6 H.sub.4 CC                                                                     CH.sub.3 H   H   30.0                                   58   amine  (CH.sub.2).sub.3 CC                                                                     CH.sub.2 (pClC.sub.6 H.sub.4)                                                          H   H   0.062                                  59   guanidine                                                                            (CH.sub.2).sub.3 CC                                                                     CH.sub.2 (pClC.sub.6 H.sub.4)                                                          H   H   0.009                                  60   amine  (CH.sub.2).sub.4 CC                                                                     CH.sub.2 (pClC.sub.6 H.sub.4)                                                          H   H   0.014                                  61   guanidine                                                                            (CH.sub.2).sub.4 CC                                                                     CH.sub.2 (pClC.sub.6 H.sub.4)                                                          H   H   0.043                                  62   amine  (CH.sub.2).sub.5                                                                        CH.sub.2 (pClC.sub.6 H.sub.4)                                                          H   H   0.176                                  63   guanidine                                                                            (CH.sub.2).sub.5                                                                        CH.sub.2 (pClC.sub.6 H.sub.4)                                                          H   H   0.011                                  64   amine  (CH.sub.2).sub.6                                                                        CH.sub.2 (pClC.sub.6 H.sub.4)                                                          H   H   0.014                                  65   guanidine                                                                            (CH.sub.2).sub.6                                                                        CH.sub.2 (pClC.sub.6 H.sub.4)                                                          H   H   0.050                                  66   amine  (CH.sub.2).sub.7                                                                        CH.sub.2 (pClC.sub.6 H.sub.4)                                                          H   H   0.026                                  67   guanidine                                                                            (CH.sub.2).sub.7                                                                        CH.sub.2 (pClC.sub.6 H.sub. 4)                                                         H   H   0.200                                  68   amine  (CH.sub.2).sub.5                                                                        CH(C.sub.6 H.sub.5).sub.2                                                              H   H   0.020(2)                               69   guanidine                                                                            (CH.sub.2).sub.5                                                                        CH(C.sub.6 H.sub.5).sub.2                                                              H   H   0.082                                  71   guanidine                                                                            (CH.sub.2).sub.3 CC                                                                     CH(C.sub.6 H.sub.5).sub.2                                                              H   H   0.008                                  72   amine  (CH.sub.2).sub.6                                                                        CH(C.sub.6 H.sub.5).sub.2                                                              H   H   0.022                                  73   amine  (CH.sub.2 CH.sub.2).sub.2 p-C.sub.6 H.sub.4                                             CH.sub.2 (pClC.sub.6 H.sub.4)                                                          H   H   0.007                                  74   guanidine                                                                            (CH.sub.2 CH.sub.2).sub.2 p-C.sub.6 H.sub.4                                             CH.sub.2 (pClC.sub.6 H.sub.4)                                                          H   H   0.019                                  75   guanidine                                                                            (CH.sub.2).sub.5                                                                        CH.sub.2 (β-napth)                                                                H   H   0.011(2)                               76   amine  (CH.sub.2).sub.5                                                                        CH.sub.2 (β-napth)                                                                H   H   0.077                                  77   guanidine                                                                            (CH.sub.2).sub.5                                                                        CH.sub.2 (α-napth)                                                               H   H   0.008                                  78   amine  (CH.sub.2).sub.5                                                                        CH.sub.2 (α-napth)                                                               H   H   0.066                                  79   guanidine                                                                            (CH.sub.2).sub.5                                                                        CH.sub.2 (pOMeC.sub.6 H.sub.4)                                                         H   H   0.011                                  80   amine  (CH.sub.2).sub.5                                                                        CH.sub.2 (pOMeC.sub.6 H.sub.4)                                                         H   H   0.160                                  81   amine  (CH.sub.2).sub.6                                                                        CH.sub.2 (pOMeC.sub.6 H.sub.4)                                                         H   H   0.023                                  82   amine  (CH.sub.2).sub.6                                                                        CH.sub.2 (α-napth)                                                               H   H   0.015                                  83   amine  (CH.sub.2).sub.6                                                                        CH.sub.2 (β-napth)                                                                H   H   0.017                                  84   guanidine                                                                            (CH.sub.2).sub.6                                                                        CH.sub.2 (pOMeC.sub.6 H.sub.4)                                                         H   H   0.024                                  85   guanidine                                                                            (CH.sub.2).sub.6                                                                        CH.sub.2 (α-napth)                                                               H   H   0.014                                  86   guanidine                                                                            (CH.sub.2).sub.6                                                                        CH.sub.2 (β-napth)                                                                H   H   0.055                                  87   amine  (CH.sub.2).sub.4 CC                                                                     CH.sub.2 (pNO.sub.2 C.sub.6 H.sub.4)                                                   H   H   0.031                                  88   guanidine                                                                            (CH.sub.2).sub.4 CC                                                                     CH.sub.2 (pNO.sub.2 C.sub.6 H.sub.4)                                                   H   H   0.031                                  89   guanidine                                                                            (CH.sub.2).sub.6                                                                        CH.sub.2 (pCF.sub.3 C6H4)                                                              H   H   0.047                                  90   amine  (CH.sub.2).sub.6                                                                        CH.sub.2 (pCF.sub.3 C6H4)                                                              H   H   0.005                                  91   guanidine                                                                            (CH.sub.2).sub.6                                                                        CH.sub.2 (mOPhC6H4)                                                                    H   H   0.009                                  92   guanidine                                                                            (CH.sub.2).sub.5                                                                        CH.sub.2 (mOPhC6H4)                                                                    H   H   0.011                                  93   guanidine                                                                            (CH.sub.2).sub.5                                                                        CH.sub.2 (pCF.sub.3 C6H4)                                                              H   H   0.014                                  94   amine  (CH.sub.2).sub.6                                                                        CH.sub.2 (mOPhC6H4)                                                                    H   H   0.009                                  95   amine  (CH.sub.2).sub.5                                                                        CH.sub.2 (mOPhC6H4)                                                                    H   H   0.108                                  96   amine  (CH.sub.2).sub.5                                                                        CH.sub.2 (pCF.sub.3 C6H4)                                                              H   H   0.186                                  97   amine  (CH.sub.2).sub.3 CC                                                                     CH.sub.2 (o,pF.sub.2 C6H4)                                                             H   H   0.130                                  98   guanidine                                                                            (CH.sub.2).sub.3 CC                                                                     CH.sub.2 (o,pF.sub.2 C6H4)                                                             H   H   0.024                                  99   amine  (CH.sub.2).sub.4 CC                                                                     CH.sub.2 (o,pF.sub.2 C6H4)                                                             H   H   0.027                                  100  guanidine                                                                            (CH.sub.2).sub.4 CC                                                                     CH.sub.2 (o,pF.sub.2 C6H4)                                                             H   H   0.025                                  101  amine  (CH.sub.2).sub.5                                                                        CH.sub.2 (o,pF.sub.2 C6H4)                                                             H   H   0.200                                  102  guanidine                                                                            (CH.sub.2).sub.5                                                                        CH.sub.2 (o,pF.sub.2 C6H4)                                                             H   H   0.016                                  103  amine  (CH.sub.2).sub.6                                                                        CH.sub.2 (o,pF.sub.2 C6H4)                                                             H   H   0.021                                  104  guanidine                                                                            (CH.sub.2).sub.6                                                                        CH.sub.2 (o,pF.sub.2 C6H4)                                                             H   H   0.038                                  105  AcNH   (CH.sub.2).sub.6                                                                        CH.sub.2 (pClC.sub.6 H.sub.4)                                                          H   H   8.5                                    __________________________________________________________________________     ##STR60##                                                                                                    IC.sub.50 (μM)                             Cmpd #     Q.sup.1 Q.sup.2                                                                        L.sup.1  n  Fg/IIbIIIa                                    __________________________________________________________________________    106        amine    (CH.sub.2).sub.3 CC                                                                    1  0.068                                         107        guanidine                                                                              (CH.sub.2).sub.3 CC                                                                    1  0.018                                         108        amine    (CH.sub.2).sub.6                                                                       1  0.012                                         109        guanidine                                                                              (CH.sub.2).sub.6                                                                       1  0.017                                         110        amine    (CH.sub.2).sub.6                                                                       2  0.008                                         111        guanidine                                                                              (CH.sub.2).sub.6                                                                       2  0.010                                         112        amine    (CH.sub.2).sub.6                                                                       3  0.008                                         113        guanidine                                                                              (CH.sub.2).sub.6                                                                       3  0.010                                         114        amine    (CH.sub.2).sub.6                                                                       4  0.008                                         115        guanidine                                                                              (CH.sub.2).sub.6                                                                       4  0.013                                         116        amine    (CH.sub.2).sub.6                                                                       5  0.011                                         117        guanidine                                                                              (CH.sub.2).sub.6                                                                       5  0.013                                         __________________________________________________________________________     ##STR61##                                                                                                   IC.sub.50 (μM)                              Cmpd #      Q.sup.1 L.sup.1 n  Fg/IIbIIIa                                     __________________________________________________________________________    118         amine   (CH.sub.2).sub.6                                                                      2  0.019                                          119         guanidine                                                                             (CH.sub.2).sub.6                                                                      2  0.013                                          __________________________________________________________________________     ##STR62##                                                                                                   IC.sub.50 (μM)                              Cmpd #      Q.sup.1 Q.sup.2                                                                       L.sup.1 n  Fg/IIbIIIa                                     __________________________________________________________________________    120         amine   (CH.sub.2).sub.6                                                                      4  0.024                                          121         guanidine                                                                             (CH.sub.2).sub.6                                                                      4  0.020                                          __________________________________________________________________________     ##STR63##                                                                                                       IC.sub.50 (μM)                          Cmpd #  Q.sup.1                                                                              L.sup.1                                                                            R.sup.22       Fg/IIbIIIa                                 __________________________________________________________________________    122     amine  (CH.sub.2).sub.6                                                                   CH.sub.2 (mNH.sub.2 C.sub.6 H.sub.4)                                                         0.012(2)                                   123     amine  (CH.sub.2).sub.6                                                                   CH.sub.2 (mNHCOBu.sup.n C.sub.6 H.sub.4)                                                     0.015(2)                                   124     guanidine                                                                            (CH.sub.2).sub.6                                                                   CH.sub.2 (mNHCOBu.sup.n C.sub.6 H.sub.4)                                                     0.012(2)                                   125     amine  (CH.sub.2).sub.6                                                                   (CH.sub.2).sub.5 NH.sub.2                                                                    0.064                                      126     guanidine                                                                            (CH.sub.2).sub.6                                                                   (CH.sub.2).sub.5 NHC(NH)NH.sub.2                                                             0.040                                      127     amine  (CH.sub.2).sub.6                                                                   CH.sub.2 (mNHCO(pgC6H4)C.sub.6 H.sub.4)                                                      0.008                                      128     amine  (CH.sub.2).sub.6                                                                   CH.sub.2 (pNH.sub.2 C.sub.6 H.sub.4)                                                         0.024                                      129     guanidine                                                                            (CH.sub.2).sub.6                                                                   (CH.sub.2).sub.4 CO.sub.2 H                               130     amine  (CH.sub.2).sub.6                                                                   (CH.sub.2).sub.4 CO.sub.2 H                               131     guanidine                                                                            (CH.sub.2).sub.5                                                                   (CH.sub. 2).sub.4 CO.sub.2 H                                                                 0.014                                      132     amine  (CH.sub.2).sub.5                                                                   (CH.sub.2).sub.4 CO.sub.2 H                                                                  0.931                                      133     guanidine                                                                            (CH.sub.2).sub.5                                                                   CH.sub.2 (pCO.sub.2 HC6H4)                                                                   0.016                                      134     guanidine                                                                            (CH.sub.2).sub.6                                                                   CH.sub.2 (pCO.sub.2 HC6H4)                                                                   0.019                                      135     amine  (CH.sub.2).sub.6                                                                   CH.sub.2 (pCO.sub.2 HC6H4)                                                                   0.008                                      136     amine  (CH.sub.2).sub.5                                                                   CH.sub.2 (pCO.sub.2 HC6H4)                                                                   0.176                                      g = NH(CNH)NH.sub.2                                                           __________________________________________________________________________     ##STR64##                                                                                                   IC.sub.50 (μM)                              Cmpd #     Q.sup.1  L.sup.1 R.sup.22                                                                         Fg/IIbIIIa                                     __________________________________________________________________________    137        amine    CH.sub.2 CC                                                                           CH.sub.3                                                                         0.351                                          138        guanidine                                                                              CH.sub.2 CC                                                                           CH.sub.3                                                                         0.009                                          139        amine    (CH.sub.2).sub.4                                                                      CH.sub.3                                                                         0.153                                          140        guanidine                                                                              (CH.sub.2).sub.4                                                                      CH.sub.3                                                                         0.069                                          __________________________________________________________________________     ##STR65##                                                                                                   IC.sub.50 (μM)                              Cmpd #      Q.sup.1 L.sup.1 R.sup.22                                                                         Fg/IIbIIIa                                     __________________________________________________________________________    141         amine   (CH.sub.2).sub.3                                                                      CH.sub.3                                                                         1.8                                            142         guanidine                                                                             (CH.sub.2).sub.3                                                                      CH.sub.3                                                                         0.068                                          143         amine   (CH.sub.2).sub.4                                                                      CH.sub.3                                                                         0.048                                          __________________________________________________________________________     ##STR66##                                                                                                       IC.sub.50 (μM)                          Cmpd #  Q.sup.1                                                                              L.sup.1    T    R.sup.21                                                                          Fg/IIbIIIa                                 __________________________________________________________________________    144     amine  (CH.sub.2).sub.3 CC                                                                      O    H   12.0                                       145     guanidine                                                                            (CH.sub.2).sub.3 CC                                                                      O    H   4.0                                        146     amine  (CH.sub.2).sub.5                                                                         O    H   80.0                                       147     guanidine                                                                            (CH.sub.2).sub.5                                                                         O    H   3.0                                        148     amine  (CH.sub.2).sub.3 CC                                                                      O    CH.sub.2 Ph                                                                       5.9                                        149     guanidine                                                                            (CH.sub.2).sub.3 CC                                                                      O    CH.sub.2 Ph                                                                       0.823                                      150     amine  p-[(CH.sub.2).sub.2 O]C.sub.6 H.sub.4                                                    O    CH.sub.2 Ph                                                                       0.119                                      151     amine  (CH.sub.2).sub.8 O                                                                       CH.sub.2                                                                           H   >100                                       152     guanidine                                                                            (CH.sub.2).sub.8 O                                                                       CH.sub.2                                                                           H   50.0                                       153     amine  (CH.sub.2).sub.3 CC                                                                      CH.sub.2                                                                           H   >100                                       154     guanidine                                                                            (CH.sub.2).sub.3 CC                                                                      CH.sub.2                                                                           H   20.0                                       155     amine  (CH.sub.2).sub.5                                                                         CH.sub.2                                                                           H   >100                                       156     guanidine                                                                            (CH.sub.2).sub.5                                                                         CH.sub.2                                                                           H   ca. 100                                    157     amidine                                                                              p-C.sub.6 H.sub.4 CH.sub.2 O                                                             CH.sub.2                                                                           H   0.137                                      __________________________________________________________________________

EXAMPLE 30 Results of ELISA and Platelet Aggregation (PA) Assays for 1,3, 4, and 7 substituted Benzodiazepinediones

    ______________________________________                                         ##STR67##                                                                

    ______________________________________                                                                       IC.sub.50 (μM)                              Cmpd #   Q.sup.1     L.sup.1   Fg/IIbIIIa                                     ______________________________________                                        158      guanidine   (CH.sub.2).sub.3                                                                        2.3                                            159      guanidine   CH.sub.2 CC                                                                             0.552                                          160      guanidine   (CH.sub.2).sub.2 CC                                                                     1.01                                           161      amine       (CH.sub.2).sub.3 CC                                                                     9.0                                            162      guanidine   (CH.sub.2).sub.3 CC                                                                     1.0                                            163      amine       (CH.sub.2).sub.4 CC                                                                     2.7                                            164      guanidine   (CH.sub.2).sub.4 CC                                                                     3.4                                            ______________________________________                                              IC.sub.50 IC.sub.50                                                                              IC.sub.50                                                  (μM)   (μM)  (μM)                                                                             PA      PA                                           Fg/       Vn/      vWF/  IC.sub.50 (μM)                                                                     IC.sub.50 (μM)                      G #   IIbIIIa   VnR      IIbIIIa                                                                             (citrate)                                                                             (heparin)                              ______________________________________                                         2    0.714     >10.0          >5.0                                           22    0.140     >10.0          8.96                                           33    0.096     >10.0    0.390 85.5                                           34     0.0036   >10.0          3.1(2)  7.5                                    35    0.013     >10.0          2.4(3)  8.0, 9.53                              36     0.0032   (3.0)     0.0004                                                                             0.94                                           27    1.9       >10.0    0.780                                                28    0.055     >10.0    0.024                                                20    0.245     >10.0    0.096                                                43    0.012     >10.0          1.7     3.34*                                  44    0.012     >10.0          8.8     14.3*                                  55    0.008     >10.0                  2.2                                    56    0.006     >10.0                  15.0                                   38    0.018                    1.19                                           42    0.009     >10.0          2.66                                           60    0.014     >10.0          2.12                                           63    0.011     >10.0          2.55                                           64    0.014     >10.0          1.20    4.76                                   66    0.026     >10.0          3.88                                           107   0.018     >10.0          0.61    0.89                                   68    0.028     >10.0          1.66    3.4                                    69    0.082     >10.0          2.09    3.9                                    71    0.008     >10.0          0.34    0.95                                   70     0.0024   >10.0          0.44    1.3                                    72    0.022     >10.0          0.46    1.1                                    108   0.012     >10.0          0.55    1.09                                   109   0.017     >10.0          1.19                                           110   0.008     >10.0          0.28    0.83                                   111   0.010     >10.0          1.14    1.49                                   73    0.007                    0.67    2.3                                    74    0.019                    1.80    4.79                                   122   0.010                    0.49                                           112   0.008                    0.40                                           113   0.010                    0.87                                           124     0.012(2)               2.76                                           123      0.015(2)              0.64                                           75      0.011(2)               6.88                                           76    0.077                    28.9                                           77    0.008                    2.65                                           78    0.066                    6.53                                           81    0.023                    0.98                                           82    0.015                    0.76                                           83    0.017                    3.19                                           84    0.024                    10.4                                           85    0.014                    6.20                                           127   0.008                    0.35                                           114   0.008                    0.31                                           115   0.018                    0.92                                           116   0.011                    0.27                                           117   0.013                    0.64                                           ______________________________________                                    

While the invention has necessarily been described in conjunction withpreferred embodiments, one of ordinary skill, after reading theforegoing specification, will be to effect various changes,substitutions of equivalents, and alterations to the subject matter setforth herein, without departing from the spirit and the scope thereof.Hence, the invention can be practiced in ways other than thosespecifically described herein. It is therefore intended that theprotection granted by Letters Patent hereon be limited only by theappended claims and the equivalents thereof.

What is claimed is:
 1. A compound represented by formula V: ##STR68##where R¹ is one to three groups independently selected from hydrogen andhalogen(F, Cl, Br, I);Q¹ is selected from the group consisting of(A) anamino group, (B) an amidino group, (C) a C₁ -C₆ aminoalkyleneiminogroup, (D) a C₁ -C₇ iminoalkyleneamino group, and (E) a guanidino group;L¹ is an optionally substituted bivalent radical selected from the groupconsisting ofC₃ -C₇ -alkylene, C₃ -C₇ -cycloalkylene, C₃ -C₇-alkenylene, C₄ -C₇ -cycloalkenylene, C₅ -C₈ -cycloalkadienylene, C₃ -C₇-alkadienylene, C₃ -C₇ -alkynylene, C₄ -C₇ -alkenynylene, C₆ -C₁₄-arylene, C₆ -C₁₄ -aryl-C₂ -C₄ -alkynylene, C₁ -C₃ -alkyl-C₆ -C₁₄-aryl-C₂ -C₄ -alkynylene, C₆ -C₁₄ -aryl-C₂ -C₄ -alkenylene, C₁ -C₃-alkyl-C₆ -C₁₄ -arylene, C₁ -C₃ -alkyl-C₆ -C₁₄ -aryl-C₂ -C₄ -alkenylene,C₆ -C₁₄ -aryl-C₁ -C₃ -alkylene, C₆ -C₁₄ -aryl-C₁ -C₃ -alkyloxyene, C₁-C₃ -alkyl-C₆ -C₁₄ -aryl-C₁ -C₂ -alkylene, C₁ -C₃ -alkyloxy-C₆ -C₁₄-arylene, C₂ -C₈ -alkyloxyene, C₁ -C₅ -alkyloxy-C₁ -C₅ -alkylene, C₆-C₁₀ -aryloxyene, C₆ -C₁₀ -aryloxy-C₁ -C₅ -alkylene, C₆ -C₁₀-arylthio-C₁ -C₅ -alkylene, ##STR69## where R¹⁴ is selected from C₂ -C₅-alkyl, C₃ -C₇ -cycloalkyl, C₂ -C₅ -alkenyl, C₃ -C₅ -alkynyl, C₆ -C₁₀-aryl, C₁ -C₂ -alkyl-C₆ -C₁₂ -aryl, C₁ -C₂ -alkyl-C₆ -C₁₀ -aryl-C₁ -C₂-alkyl, C₆ -C₁₀ -aryl-C₁ -C₂ -alkyl, and C₆ -C₁₀ -aryloxy-C₁ -C₂ -alkyl;R¹⁵ is chemical bond connecting L¹ to position 8 of the benzazepine-one;R¹⁶ is selected fromC₂ -C₅ -alkyl, C₃ -C₇ -cycloalkyl, C₃ -C₅ -alkenyl,C₃ -C₅ -alkynyl, C₆ -C₁₀ -aryl, C₁ -C₃ -alkyl-C₆ -C₁₂ -aryl, and C₆ -C₁₀-aryl-C₁ -C₂ -alkyl, wherein R¹⁴ and R¹⁶ bond L¹ to Q¹, and where thesubstituents are selected from the group hydrogen, halo(F, Cl, Br, I),C₁ -C₄ alkoxy, C₁ -C₄ alkyl, phenyl, benzyl, and halo(F, Cl, Br, I)-C₁-C₄ alkyl; R²⁰ is hydrogen; R²¹ is selected from the group consisting of(i) hydrogen, (ii) optionally substituted C₁ -C₁₂ -alkyl, (iii)optionally substituted C₆ -C₁₄ -aryl, (iv) optionally substituted C₃-C₁₄ -cycloalkyl, (v) optionally substituted C₁ -C₁₂ -alkyl-C₆ -C₁₄-aryl, (vi) optionally substituted C₁ -C₁₂ -alkyl-C₃ -C₁₄ -cycloalkyl,where the substituents are selected from (a) halo (F, Cl, Br, I), (b)nitro, (c) hydroxy, (d) carboxy, (e) tetrazole, (f) hydroxamate, (g)sulfonamide, (h) trifluoroimide, (i) phosphonate, (j) C₁ -C₆ -alkyl, (k)C₆ -C₁₄ -aryl, (l) benzyl, (m) C₃ -C₁₄ -cycloalkyl, (n) COR²⁴ where R²⁴is selected from the group C₁ -C₈ -alkoxy, C₃ -C₁₂ -alkenoxy, C₆ -C₁₂-aryloxy, di-C₁ -C₈ -alkylamino-C₁ -C₈ -alkoxy, alkanoylamino-C₁ -C₈-alkoxy selected from the group acetylaminoethoxy,nicotinoylaminoethoxy, uccinamidoethoxy, and pivaloyloxyethoxy, and C₆-C₁₂ -aryl-C₁ -C₈ -alkoxy where the aryl group is unsubstituted orsubstituted with one to three of the groups nitro, halo (F, Cl, Br, I),C₁ -C₄ -alkoxy, amino, hydroxy, hydroxy-C₂ -C₈ -alkoxy, and dihydroxy-C₃-C₈ -alkoxy, (o) CONR²⁵ R²⁶ where R²⁵ and R²⁶ are independently selectedfrom hydrogen, C₁ -C₁₀ -alkyl, C₃ -C₁₀ -alkenyl, C₆ -C₁₄ -aryl, C₁ -C₆-alkyl-C₆ -C₁₀ -aryl, optionally R²⁵ and R²⁶ taken together may formtrimethylene, tetramethylene, pentamethylene, and 3-oxopentamethylene,and (vii) Q² --L³ -- where Q² is selected from hydrogen and Q¹, and L³is selected from a chemical bond and L¹ where R¹⁵ bonds L¹ to position 4of the benzazepine-one; D is selected from the group consisting of R²¹,and --(C═O)--Xaa, where Xaa is one to three D or L α-amino acidresidues; R²⁸ is selected from the group consisting of (i) hydroxy, (ii)C₁ -C₈ -alkoxy, (iii) C₃ -C₁₂ -alkenoxy, (iv) C₆ -C₁₂ -aryloxy, (v) C₁-C₆ -alkyl-C₆ -C₁₂ -aryloxy, (vi) di-C₁ -C₈ -alkylamino-C₁ -C₈ -alkoxy,(vii) acylamino-C₁ -C₈ -alkoxy selected from the group (a)acetylaminoethoxy, (b) nicotinoylaminoethoxy, and (c) succinamidoethoxy,(viii) C₁ -C₈ -alkanoyloxy-C₁ -C₈ -alkoxy, (ix) C₆ -C₁₂ -aryl-C₁ -C₈-alkoxy where the aryl group is unsubstituted or substituted with one tothree of the groups (a) nitro, (b) halo (F, Cl, Br, I), (c) C₁ -C₄-alkoxy, and (d) amino, (x) hydroxy-C₂ -C₈ -alkoxy, (xi) dihydroxy-C₃-C₈ -alkoxy, and (xii) NR²⁹ R³⁰ where R²⁹ and R³⁰ are independentlyselected from the group (a) hydrogen, (b) C₁ -C₈ -alkyl, (c) C₃ -C₈-alkenyl, (d) C₆ -C₁₂ -aryl where the aryl group is unsubstituted orsubstituted with one to three of the groups nitro, halo (F, Cl, Br, I),C₁ -C₄ -alkoxy, and amino, and (e) C₆ -C₁₂ -aryl-C₁ -C₈ -alkyl where thearyl group is unsubstituted or substituted with one to three of thegroups nitro, halo (F, Cl, Br, I), and C₁ -C₄ -alkoxy;andpharmaceutically acceptable salts thereof.